ES2963613T3 - Compuestos terapéuticos - Google Patents
Compuestos terapéuticos Download PDFInfo
- Publication number
- ES2963613T3 ES2963613T3 ES19795615T ES19795615T ES2963613T3 ES 2963613 T3 ES2963613 T3 ES 2963613T3 ES 19795615 T ES19795615 T ES 19795615T ES 19795615 T ES19795615 T ES 19795615T ES 2963613 T3 ES2963613 T3 ES 2963613T3
- Authority
- ES
- Spain
- Prior art keywords
- methyl
- acid
- carboxylic
- carbon
- methoxy
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 273
- 230000001225 therapeutic effect Effects 0.000 title description 8
- 102100031701 Nuclear factor erythroid 2-related factor 2 Human genes 0.000 claims abstract description 87
- 101000588302 Homo sapiens Nuclear factor erythroid 2-related factor 2 Proteins 0.000 claims abstract description 86
- 238000011282 treatment Methods 0.000 claims abstract description 45
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 41
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 30
- 201000010099 disease Diseases 0.000 claims abstract description 23
- 230000004913 activation Effects 0.000 claims abstract description 21
- 208000035475 disorder Diseases 0.000 claims abstract description 17
- 239000002253 acid Substances 0.000 claims description 595
- 229910052799 carbon Inorganic materials 0.000 claims description 463
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 229
- -1 3-trifluoromethyl-1,2,4-triazole-5- yl Chemical group 0.000 claims description 140
- 125000000623 heterocyclic group Chemical group 0.000 claims description 102
- 125000001424 substituent group Chemical group 0.000 claims description 97
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 93
- 125000001072 heteroaryl group Chemical group 0.000 claims description 92
- 125000000217 alkyl group Chemical group 0.000 claims description 82
- 125000003545 alkoxy group Chemical group 0.000 claims description 70
- 229910052736 halogen Inorganic materials 0.000 claims description 67
- 150000002367 halogens Chemical class 0.000 claims description 66
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 57
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 57
- 229910052739 hydrogen Inorganic materials 0.000 claims description 53
- 150000003839 salts Chemical class 0.000 claims description 53
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 51
- 239000001257 hydrogen Substances 0.000 claims description 51
- 229910052757 nitrogen Inorganic materials 0.000 claims description 44
- 125000001188 haloalkyl group Chemical group 0.000 claims description 42
- 125000003118 aryl group Chemical group 0.000 claims description 38
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 34
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 31
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 claims description 29
- 229920006395 saturated elastomer Polymers 0.000 claims description 29
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 28
- 208000008338 non-alcoholic fatty liver disease Diseases 0.000 claims description 27
- 208000020832 chronic kidney disease Diseases 0.000 claims description 26
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 23
- 206010012601 diabetes mellitus Diseases 0.000 claims description 21
- 208000007056 sickle cell anemia Diseases 0.000 claims description 21
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 18
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims description 18
- 125000002947 alkylene group Chemical group 0.000 claims description 18
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 16
- 206010064911 Pulmonary arterial hypertension Diseases 0.000 claims description 16
- 206010053219 non-alcoholic steatohepatitis Diseases 0.000 claims description 16
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 15
- 206010064930 age-related macular degeneration Diseases 0.000 claims description 14
- MNWFXJYAOYHMED-UHFFFAOYSA-N heptanoic acid Chemical compound CCCCCCC(O)=O MNWFXJYAOYHMED-UHFFFAOYSA-N 0.000 claims description 14
- 208000002780 macular degeneration Diseases 0.000 claims description 14
- 208000024412 Friedreich ataxia Diseases 0.000 claims description 13
- 125000004429 atom Chemical group 0.000 claims description 13
- 150000001721 carbon Chemical group 0.000 claims description 13
- 125000001153 fluoro group Chemical group F* 0.000 claims description 13
- 229910052717 sulfur Inorganic materials 0.000 claims description 13
- 239000011593 sulfur Substances 0.000 claims description 13
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 claims description 12
- 208000010159 IgA glomerulonephritis Diseases 0.000 claims description 12
- 206010021263 IgA nephropathy Diseases 0.000 claims description 12
- 208000032851 Subarachnoid Hemorrhage Diseases 0.000 claims description 12
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 12
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims description 12
- 239000000460 chlorine Chemical group 0.000 claims description 12
- ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 claims description 12
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 claims description 12
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 11
- 125000005842 heteroatom Chemical group 0.000 claims description 11
- 229910052760 oxygen Inorganic materials 0.000 claims description 11
- 239000001301 oxygen Substances 0.000 claims description 11
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 claims description 10
- 125000004432 carbon atom Chemical group C* 0.000 claims description 10
- 208000019423 liver disease Diseases 0.000 claims description 10
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 10
- 206010009900 Colitis ulcerative Diseases 0.000 claims description 9
- 208000011231 Crohn disease Diseases 0.000 claims description 9
- 206010016654 Fibrosis Diseases 0.000 claims description 9
- 208000032382 Ischaemic stroke Diseases 0.000 claims description 9
- 201000006704 Ulcerative Colitis Diseases 0.000 claims description 9
- 230000001404 mediated effect Effects 0.000 claims description 9
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 9
- 206010008111 Cerebral haemorrhage Diseases 0.000 claims description 8
- 206010019280 Heart failures Diseases 0.000 claims description 8
- 230000000747 cardiac effect Effects 0.000 claims description 8
- 230000001684 chronic effect Effects 0.000 claims description 8
- 230000007882 cirrhosis Effects 0.000 claims description 8
- 208000019425 cirrhosis of liver Diseases 0.000 claims description 8
- 208000020658 intracerebral hemorrhage Diseases 0.000 claims description 8
- 125000001800 methanetriyl group Chemical group C(*)(*)* 0.000 claims description 8
- 125000004043 oxo group Chemical group O=* 0.000 claims description 8
- 201000001320 Atherosclerosis Diseases 0.000 claims description 7
- 208000010061 Autosomal Dominant Polycystic Kidney Diseases 0.000 claims description 7
- 208000001145 Metabolic Syndrome Diseases 0.000 claims description 7
- 208000008589 Obesity Diseases 0.000 claims description 7
- 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 claims description 7
- 208000022185 autosomal dominant polycystic kidney disease Diseases 0.000 claims description 7
- 208000005980 beta thalassemia Diseases 0.000 claims description 7
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 7
- 229910052805 deuterium Inorganic materials 0.000 claims description 7
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 7
- 235000020824 obesity Nutrition 0.000 claims description 7
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 7
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 7
- NEAQRZUHTPSBBM-UHFFFAOYSA-N 2-hydroxy-3,3-dimethyl-7-nitro-4h-isoquinolin-1-one Chemical class C1=C([N+]([O-])=O)C=C2C(=O)N(O)C(C)(C)CC2=C1 NEAQRZUHTPSBBM-UHFFFAOYSA-N 0.000 claims description 6
- 125000006163 5-membered heteroaryl group Chemical group 0.000 claims description 6
- 208000024985 Alport syndrome Diseases 0.000 claims description 6
- 206010007572 Cardiac hypertrophy Diseases 0.000 claims description 6
- 208000006029 Cardiomegaly Diseases 0.000 claims description 6
- 201000003883 Cystic fibrosis Diseases 0.000 claims description 6
- 206010012438 Dermatitis atopic Diseases 0.000 claims description 6
- 208000032781 Diabetic cardiomyopathy Diseases 0.000 claims description 6
- 201000011240 Frontotemporal dementia Diseases 0.000 claims description 6
- 206010019799 Hepatitis viral Diseases 0.000 claims description 6
- 208000023105 Huntington disease Diseases 0.000 claims description 6
- 206010020772 Hypertension Diseases 0.000 claims description 6
- 201000009794 Idiopathic Pulmonary Fibrosis Diseases 0.000 claims description 6
- 206010022489 Insulin Resistance Diseases 0.000 claims description 6
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 6
- 208000010718 Multiple Organ Failure Diseases 0.000 claims description 6
- 208000018737 Parkinson disease Diseases 0.000 claims description 6
- 201000004681 Psoriasis Diseases 0.000 claims description 6
- 206010046851 Uveitis Diseases 0.000 claims description 6
- 206010069351 acute lung injury Diseases 0.000 claims description 6
- 206010003119 arrhythmia Diseases 0.000 claims description 6
- 201000008937 atopic dermatitis Diseases 0.000 claims description 6
- 229910052801 chlorine Chemical group 0.000 claims description 6
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 6
- 208000003215 hereditary nephritis Diseases 0.000 claims description 6
- 208000036971 interstitial lung disease 2 Diseases 0.000 claims description 6
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 6
- 201000005202 lung cancer Diseases 0.000 claims description 6
- 208000020816 lung neoplasm Diseases 0.000 claims description 6
- 208000029744 multiple organ dysfunction syndrome Diseases 0.000 claims description 6
- 208000010125 myocardial infarction Diseases 0.000 claims description 6
- 208000005069 pulmonary fibrosis Diseases 0.000 claims description 6
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 6
- 208000006934 radiodermatitis Diseases 0.000 claims description 6
- 238000007634 remodeling Methods 0.000 claims description 6
- 230000008439 repair process Effects 0.000 claims description 6
- 238000002560 therapeutic procedure Methods 0.000 claims description 6
- 239000003053 toxin Substances 0.000 claims description 6
- 231100000765 toxin Toxicity 0.000 claims description 6
- 108700012359 toxins Proteins 0.000 claims description 6
- 201000001862 viral hepatitis Diseases 0.000 claims description 6
- 206010006187 Breast cancer Diseases 0.000 claims description 5
- 208000026310 Breast neoplasm Diseases 0.000 claims description 5
- 206010009944 Colon cancer Diseases 0.000 claims description 5
- 208000007342 Diabetic Nephropathies Diseases 0.000 claims description 5
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims description 5
- 125000001246 bromo group Chemical group Br* 0.000 claims description 5
- 239000011203 carbon fibre reinforced carbon Substances 0.000 claims description 5
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 5
- 208000029742 colonic neoplasm Diseases 0.000 claims description 5
- 208000033679 diabetic kidney disease Diseases 0.000 claims description 5
- 208000002551 irritable bowel syndrome Diseases 0.000 claims description 5
- 201000006417 multiple sclerosis Diseases 0.000 claims description 5
- 125000002971 oxazolyl group Chemical group 0.000 claims description 5
- 125000001399 1,2,3-triazolyl group Chemical group N1N=NC(=C1)* 0.000 claims description 4
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 claims description 4
- 208000024827 Alzheimer disease Diseases 0.000 claims description 4
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 4
- 208000033051 Fuchs endothelial corneal dystrophy Diseases 0.000 claims description 4
- 208000013616 Respiratory Distress Syndrome Diseases 0.000 claims description 4
- 229940100389 Sulfonylurea Drugs 0.000 claims description 4
- 229940123464 Thiazolidinedione Drugs 0.000 claims description 4
- 201000000028 adult respiratory distress syndrome Diseases 0.000 claims description 4
- 208000038003 heart failure with preserved ejection fraction Diseases 0.000 claims description 4
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 4
- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 claims description 4
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 4
- 125000003386 piperidinyl group Chemical group 0.000 claims description 4
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 4
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 4
- 125000004076 pyridyl group Chemical group 0.000 claims description 4
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 4
- ZOBPZXTWZATXDG-UHFFFAOYSA-N 1,3-thiazolidine-2,4-dione Chemical compound O=C1CSC(=O)N1 ZOBPZXTWZATXDG-UHFFFAOYSA-N 0.000 claims description 3
- RUXHWBMJNBBYNL-UHFFFAOYSA-N 3-hydroxy-1,2-dihydropyrrol-5-one Chemical compound OC1=CC(=O)NC1 RUXHWBMJNBBYNL-UHFFFAOYSA-N 0.000 claims description 3
- WVVZEEAORNADKL-UHFFFAOYSA-N 3h-oxathiadiazole 2-oxide Chemical compound O=S1NN=CO1 WVVZEEAORNADKL-UHFFFAOYSA-N 0.000 claims description 3
- CTQPPUPWHLGKOB-UHFFFAOYSA-N 4h-oxadiazol-5-one Chemical compound O=C1CN=NO1 CTQPPUPWHLGKOB-UHFFFAOYSA-N 0.000 claims description 3
- RXSFZYSNXZGVCU-UHFFFAOYSA-N 4h-oxadiazole-5-thione Chemical compound S=C1CN=NO1 RXSFZYSNXZGVCU-UHFFFAOYSA-N 0.000 claims description 3
- XMBRHWVCMOPSRW-UHFFFAOYSA-N 4h-thiadiazol-5-one Chemical compound O=C1CN=NS1 XMBRHWVCMOPSRW-UHFFFAOYSA-N 0.000 claims description 3
- 150000007945 N-acyl ureas Chemical class 0.000 claims description 3
- 150000007513 acids Chemical class 0.000 claims description 3
- 125000004603 benzisoxazolyl group Chemical group O1N=C(C2=C1C=CC=C2)* 0.000 claims description 3
- LOGSONSNCYTHPS-UHFFFAOYSA-N cyclopentane-1,3-dione Chemical class O=C1CCC(=O)C1 LOGSONSNCYTHPS-UHFFFAOYSA-N 0.000 claims description 3
- 206010061989 glomerulosclerosis Diseases 0.000 claims description 3
- COWNFYYYZFRNOY-UHFFFAOYSA-N oxazolidinedione Chemical compound O=C1COC(=O)N1 COWNFYYYZFRNOY-UHFFFAOYSA-N 0.000 claims description 3
- 150000003009 phosphonic acids Chemical class 0.000 claims description 3
- 150000003455 sulfinic acids Chemical class 0.000 claims description 3
- 229940124530 sulfonamide Drugs 0.000 claims description 3
- 150000003456 sulfonamides Chemical class 0.000 claims description 3
- 150000003460 sulfonic acids Chemical class 0.000 claims description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 3
- 125000004504 1,2,4-oxadiazolyl group Chemical group 0.000 claims description 2
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 claims description 2
- 125000003354 benzotriazolyl group Chemical group N1N=NC2=C1C=CC=C2* 0.000 claims description 2
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 claims description 2
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 2
- 125000004857 imidazopyridinyl group Chemical group N1C(=NC2=C1C=CC=N2)* 0.000 claims description 2
- 125000004575 3-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims 3
- 125000004938 5-pyridyl group Chemical group N1=CC=CC(=C1)* 0.000 claims 1
- 125000004939 6-pyridyl group Chemical group N1=CC=CC=C1* 0.000 claims 1
- RGSFGYAAUTVSQA-UHFFFAOYSA-N Cyclopentane Chemical compound C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 claims 1
- 208000024716 acute asthma Diseases 0.000 claims 1
- 125000000336 imidazol-5-yl group Chemical group [H]N1C([H])=NC([H])=C1[*] 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 122
- 239000012190 activator Substances 0.000 abstract description 20
- 238000002360 preparation method Methods 0.000 abstract description 5
- 230000008569 process Effects 0.000 abstract description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 205
- 239000000543 intermediate Substances 0.000 description 143
- 239000000203 mixture Substances 0.000 description 136
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 133
- 239000000243 solution Substances 0.000 description 121
- 239000011541 reaction mixture Substances 0.000 description 94
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 84
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 82
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 81
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 69
- 238000000746 purification Methods 0.000 description 68
- 235000019439 ethyl acetate Nutrition 0.000 description 66
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 62
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 57
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 57
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 55
- 150000002894 organic compounds Chemical class 0.000 description 54
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 42
- 238000005160 1H NMR spectroscopy Methods 0.000 description 41
- 239000007787 solid Substances 0.000 description 41
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 40
- 239000012267 brine Substances 0.000 description 40
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 40
- 239000011734 sodium Substances 0.000 description 39
- 238000006243 chemical reaction Methods 0.000 description 35
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Natural products OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 35
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 32
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 31
- 229910052786 argon Inorganic materials 0.000 description 31
- 238000003818 flash chromatography Methods 0.000 description 30
- 239000000377 silicon dioxide Substances 0.000 description 30
- 239000000725 suspension Substances 0.000 description 30
- 238000001914 filtration Methods 0.000 description 27
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 26
- 239000000706 filtrate Substances 0.000 description 25
- NZNMSOFKMUBTKW-UHFFFAOYSA-N cyclohexanecarboxylic acid Chemical compound OC(=O)C1CCCCC1 NZNMSOFKMUBTKW-UHFFFAOYSA-N 0.000 description 24
- 239000002244 precipitate Substances 0.000 description 24
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 22
- 239000003814 drug Substances 0.000 description 20
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 19
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 18
- LDCRTTXIJACKKU-ONEGZZNKSA-N dimethyl fumarate Chemical compound COC(=O)\C=C\C(=O)OC LDCRTTXIJACKKU-ONEGZZNKSA-N 0.000 description 17
- 125000006239 protecting group Chemical group 0.000 description 16
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 16
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 15
- 229960004419 dimethyl fumarate Drugs 0.000 description 15
- 239000010410 layer Substances 0.000 description 15
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 15
- 239000012044 organic layer Substances 0.000 description 15
- 230000036542 oxidative stress Effects 0.000 description 15
- 239000000651 prodrug Substances 0.000 description 15
- 229940002612 prodrug Drugs 0.000 description 15
- 235000017557 sodium bicarbonate Nutrition 0.000 description 15
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 15
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 14
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 14
- 238000010992 reflux Methods 0.000 description 14
- 238000005481 NMR spectroscopy Methods 0.000 description 13
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 13
- 208000006673 asthma Diseases 0.000 description 13
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 13
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 13
- 238000003786 synthesis reaction Methods 0.000 description 13
- 241001465754 Metazoa Species 0.000 description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- 238000001727 in vivo Methods 0.000 description 12
- 150000002148 esters Chemical class 0.000 description 11
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 11
- 235000019341 magnesium sulphate Nutrition 0.000 description 11
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 10
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 10
- 239000012043 crude product Substances 0.000 description 10
- 239000003112 inhibitor Substances 0.000 description 10
- 239000012279 sodium borohydride Substances 0.000 description 10
- 229910000033 sodium borohydride Inorganic materials 0.000 description 10
- 229910052938 sodium sulfate Inorganic materials 0.000 description 10
- 235000011152 sodium sulphate Nutrition 0.000 description 10
- 239000007832 Na2SO4 Substances 0.000 description 9
- 125000002619 bicyclic group Chemical group 0.000 description 9
- 230000015572 biosynthetic process Effects 0.000 description 9
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 9
- 238000007429 general method Methods 0.000 description 9
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 9
- 238000003756 stirring Methods 0.000 description 9
- 229940124597 therapeutic agent Drugs 0.000 description 9
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 8
- 101150116862 KEAP1 gene Proteins 0.000 description 8
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 8
- 150000001408 amides Chemical class 0.000 description 8
- 150000001412 amines Chemical group 0.000 description 8
- 239000008346 aqueous phase Substances 0.000 description 8
- 239000003153 chemical reaction reagent Substances 0.000 description 8
- 230000000694 effects Effects 0.000 description 8
- 201000005206 focal segmental glomerulosclerosis Diseases 0.000 description 8
- 231100000854 focal segmental glomerulosclerosis Toxicity 0.000 description 8
- 230000014509 gene expression Effects 0.000 description 8
- 230000001965 increasing effect Effects 0.000 description 8
- 238000004519 manufacturing process Methods 0.000 description 8
- 239000003607 modifier Substances 0.000 description 8
- AQRLNPVMDITEJU-UHFFFAOYSA-N triethylsilane Chemical compound CC[SiH](CC)CC AQRLNPVMDITEJU-UHFFFAOYSA-N 0.000 description 8
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 7
- 206010061218 Inflammation Diseases 0.000 description 7
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 7
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 7
- 150000001204 N-oxides Chemical class 0.000 description 7
- 230000001154 acute effect Effects 0.000 description 7
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 7
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 7
- 239000003795 chemical substances by application Substances 0.000 description 7
- 230000004054 inflammatory process Effects 0.000 description 7
- 125000002950 monocyclic group Chemical group 0.000 description 7
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 7
- 239000007858 starting material Substances 0.000 description 7
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 6
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 6
- 108010018924 Heme Oxygenase-1 Proteins 0.000 description 6
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 6
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 6
- 206010028980 Neoplasm Diseases 0.000 description 6
- 125000002252 acyl group Chemical group 0.000 description 6
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 6
- 235000019253 formic acid Nutrition 0.000 description 6
- CPELXLSAUQHCOX-UHFFFAOYSA-N hydrogen bromide Substances Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 6
- 238000002347 injection Methods 0.000 description 6
- 239000007924 injection Substances 0.000 description 6
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 6
- QAWFLJGZSZIZHO-UHFFFAOYSA-N methyl 4-bromobutanoate Chemical compound COC(=O)CCCBr QAWFLJGZSZIZHO-UHFFFAOYSA-N 0.000 description 6
- 239000012071 phase Substances 0.000 description 6
- XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical compound C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 description 6
- SUVMJBTUFCVSAD-UHFFFAOYSA-N sulforaphane Chemical compound CS(=O)CCCCN=C=S SUVMJBTUFCVSAD-UHFFFAOYSA-N 0.000 description 6
- 208000024891 symptom Diseases 0.000 description 6
- WPTTVJLTNAWYAO-KPOXMGGZSA-N Bardoxolone methyl Chemical group C([C@@]12C)=C(C#N)C(=O)C(C)(C)[C@@H]1CC[C@]1(C)C2=CC(=O)[C@@H]2[C@@H]3CC(C)(C)CC[C@]3(C(=O)OC)CC[C@]21C WPTTVJLTNAWYAO-KPOXMGGZSA-N 0.000 description 5
- 239000007821 HATU Substances 0.000 description 5
- 102100028006 Heme oxygenase 1 Human genes 0.000 description 5
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 5
- 230000002378 acidificating effect Effects 0.000 description 5
- 230000003213 activating effect Effects 0.000 description 5
- 210000004556 brain Anatomy 0.000 description 5
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 5
- 229910052794 bromium Inorganic materials 0.000 description 5
- 201000011510 cancer Diseases 0.000 description 5
- 210000004027 cell Anatomy 0.000 description 5
- 239000003085 diluting agent Substances 0.000 description 5
- 239000002552 dosage form Substances 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- 239000003480 eluent Substances 0.000 description 5
- 239000012530 fluid Substances 0.000 description 5
- 230000006870 function Effects 0.000 description 5
- 125000000592 heterocycloalkyl group Chemical group 0.000 description 5
- 230000000302 ischemic effect Effects 0.000 description 5
- 239000007788 liquid Substances 0.000 description 5
- 239000012280 lithium aluminium hydride Substances 0.000 description 5
- OKKJLVBELUTLKV-VMNATFBRSA-N methanol-d1 Chemical compound [2H]OC OKKJLVBELUTLKV-VMNATFBRSA-N 0.000 description 5
- PNDWPPJIBOBEOE-UHFFFAOYSA-N methyl 2-[1-(bromomethyl)cyclopropyl]acetate Chemical compound COC(=O)CC1(CBr)CC1 PNDWPPJIBOBEOE-UHFFFAOYSA-N 0.000 description 5
- 208000015122 neurodegenerative disease Diseases 0.000 description 5
- 230000037361 pathway Effects 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 230000001681 protective effect Effects 0.000 description 5
- 108090000623 proteins and genes Proteins 0.000 description 5
- 150000003384 small molecules Chemical class 0.000 description 5
- 125000003039 tetrahydroisoquinolinyl group Chemical class C1(NCCC2=CC=CC=C12)* 0.000 description 5
- 239000003643 water by type Substances 0.000 description 5
- FCYUPOCBNOAMHF-HFEGYEGKSA-N (1R)-1-phenylethanamine Chemical compound C[C@@H](N)c1ccccc1.C[C@@H](N)c1ccccc1 FCYUPOCBNOAMHF-HFEGYEGKSA-N 0.000 description 4
- YOETUEMZNOLGDB-UHFFFAOYSA-N 2-methylpropyl carbonochloridate Chemical compound CC(C)COC(Cl)=O YOETUEMZNOLGDB-UHFFFAOYSA-N 0.000 description 4
- JWUJQDFVADABEY-UHFFFAOYSA-N 2-methyltetrahydrofuran Chemical compound CC1CCCO1 JWUJQDFVADABEY-UHFFFAOYSA-N 0.000 description 4
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 4
- 208000009304 Acute Kidney Injury Diseases 0.000 description 4
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 4
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 4
- YNQLUTRBYVCPMQ-UHFFFAOYSA-N Ethylbenzene Chemical compound CCC1=CC=CC=C1 YNQLUTRBYVCPMQ-UHFFFAOYSA-N 0.000 description 4
- 241000699670 Mus sp. Species 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- 208000033626 Renal failure acute Diseases 0.000 description 4
- 108010016797 Sickle Hemoglobin Proteins 0.000 description 4
- 208000006011 Stroke Diseases 0.000 description 4
- 239000004480 active ingredient Substances 0.000 description 4
- 201000011040 acute kidney failure Diseases 0.000 description 4
- 150000003973 alkyl amines Chemical class 0.000 description 4
- 125000003277 amino group Chemical group 0.000 description 4
- 239000005557 antagonist Substances 0.000 description 4
- 239000003963 antioxidant agent Substances 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 4
- 239000012298 atmosphere Substances 0.000 description 4
- 230000009286 beneficial effect Effects 0.000 description 4
- 230000008901 benefit Effects 0.000 description 4
- 239000003054 catalyst Substances 0.000 description 4
- 238000002648 combination therapy Methods 0.000 description 4
- 230000001120 cytoprotective effect Effects 0.000 description 4
- YWEUIGNSBFLMFL-UHFFFAOYSA-N diphosphonate Chemical compound O=P(=O)OP(=O)=O YWEUIGNSBFLMFL-UHFFFAOYSA-N 0.000 description 4
- 239000012065 filter cake Substances 0.000 description 4
- 238000000227 grinding Methods 0.000 description 4
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 4
- 230000000155 isotopic effect Effects 0.000 description 4
- UOPFIWYXBIHPIP-SFTDATJTSA-N n-[(1s,2s)-2-amino-1,2-diphenylethyl]-4-methylbenzenesulfonamide Chemical compound C1=CC(C)=CC=C1S(=O)(=O)N[C@@H](C=1C=CC=CC=1)[C@@H](N)C1=CC=CC=C1 UOPFIWYXBIHPIP-SFTDATJTSA-N 0.000 description 4
- 239000012074 organic phase Substances 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 230000002265 prevention Effects 0.000 description 4
- LOUPRKONTZGTKE-LHHVKLHASA-N quinidine Chemical compound C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@H]2[C@@H](O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-LHHVKLHASA-N 0.000 description 4
- 229910000029 sodium carbonate Inorganic materials 0.000 description 4
- 235000017550 sodium carbonate Nutrition 0.000 description 4
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 4
- PAJMKGZZBBTTOY-ZFORQUDYSA-N treprostinil Chemical compound C1=CC=C(OCC(O)=O)C2=C1C[C@@H]1[C@@H](CC[C@@H](O)CCCCC)[C@H](O)C[C@@H]1C2 PAJMKGZZBBTTOY-ZFORQUDYSA-N 0.000 description 4
- RQEUFEKYXDPUSK-SSDOTTSWSA-N (1R)-1-phenylethanamine Chemical compound C[C@@H](N)C1=CC=CC=C1 RQEUFEKYXDPUSK-SSDOTTSWSA-N 0.000 description 3
- RNKOUSCCPHSCFE-UHFFFAOYSA-N (2,4-dimethoxyphenyl)methanol Chemical compound COC1=CC=C(CO)C(OC)=C1 RNKOUSCCPHSCFE-UHFFFAOYSA-N 0.000 description 3
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 3
- KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
- SUVMJBTUFCVSAD-JTQLQIEISA-N 4-Methylsulfinylbutyl isothiocyanate Natural products C[S@](=O)CCCCN=C=S SUVMJBTUFCVSAD-JTQLQIEISA-N 0.000 description 3
- RMZYHRQIGZSXQM-UHFFFAOYSA-N 5-(difluoromethyl)-1-methyltriazole-4-carboxylic acid Chemical compound CN1N=NC(C(O)=O)=C1C(F)F RMZYHRQIGZSXQM-UHFFFAOYSA-N 0.000 description 3
- 108700032225 Antioxidant Response Elements Proteins 0.000 description 3
- 206010003591 Ataxia Diseases 0.000 description 3
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- 108090000695 Cytokines Proteins 0.000 description 3
- 102000004127 Cytokines Human genes 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 3
- 239000002841 Lewis acid Substances 0.000 description 3
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 3
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
- 241000699666 Mus <mouse, genus> Species 0.000 description 3
- 108091023040 Transcription factor Proteins 0.000 description 3
- 102000040945 Transcription factor Human genes 0.000 description 3
- OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 3
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 3
- 239000000443 aerosol Substances 0.000 description 3
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 3
- 229910021529 ammonia Inorganic materials 0.000 description 3
- 238000010171 animal model Methods 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 3
- 238000007796 conventional method Methods 0.000 description 3
- 125000004122 cyclic group Chemical group 0.000 description 3
- 230000006378 damage Effects 0.000 description 3
- 230000002950 deficient Effects 0.000 description 3
- 230000018109 developmental process Effects 0.000 description 3
- 239000006196 drop Substances 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 125000005843 halogen group Chemical group 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 3
- 230000007062 hydrolysis Effects 0.000 description 3
- 238000006460 hydrolysis reaction Methods 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 230000006872 improvement Effects 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 210000004347 intestinal mucosa Anatomy 0.000 description 3
- 208000001286 intracranial vasospasm Diseases 0.000 description 3
- 238000007918 intramuscular administration Methods 0.000 description 3
- 238000007912 intraperitoneal administration Methods 0.000 description 3
- 238000001990 intravenous administration Methods 0.000 description 3
- 210000001503 joint Anatomy 0.000 description 3
- 208000017169 kidney disease Diseases 0.000 description 3
- 238000011813 knockout mouse model Methods 0.000 description 3
- 150000007517 lewis acids Chemical class 0.000 description 3
- 230000000670 limiting effect Effects 0.000 description 3
- 108020004999 messenger RNA Proteins 0.000 description 3
- 208000030159 metabolic disease Diseases 0.000 description 3
- 238000010172 mouse model Methods 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 230000004770 neurodegeneration Effects 0.000 description 3
- LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 description 3
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 3
- 210000000056 organ Anatomy 0.000 description 3
- 229910052763 palladium Inorganic materials 0.000 description 3
- 230000000144 pharmacologic effect Effects 0.000 description 3
- DLYUQMMRRRQYAE-UHFFFAOYSA-N phosphorus pentoxide Inorganic materials O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 3
- 125000005543 phthalimide group Chemical group 0.000 description 3
- 239000003642 reactive oxygen metabolite Substances 0.000 description 3
- BNRNXUUZRGQAQC-UHFFFAOYSA-N sildenafil Chemical compound CCCC1=NN(C)C(C(N2)=O)=C1N=C2C(C(=CC=1)OCC)=CC=1S(=O)(=O)N1CCN(C)CC1 BNRNXUUZRGQAQC-UHFFFAOYSA-N 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 238000001228 spectrum Methods 0.000 description 3
- 238000006467 substitution reaction Methods 0.000 description 3
- 229960005559 sulforaphane Drugs 0.000 description 3
- 235000015487 sulforaphane Nutrition 0.000 description 3
- 238000010189 synthetic method Methods 0.000 description 3
- 239000003826 tablet Substances 0.000 description 3
- 230000008685 targeting Effects 0.000 description 3
- 125000005958 tetrahydrothienyl group Chemical group 0.000 description 3
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
- VXBNTHRZPJLRSS-PTCSXESPSA-N (2s)-2-[(2r,3r,4s,5s,6r)-3-benzoyloxy-2-[(1r,2r,3s,5r)-3-[(2,4-dioxo-1h-pyrimidine-6-carbonyl)amino]-5-[2-[[2-[2-[2-oxo-2-[(3,6,8-trisulfonaphthalen-1-yl)amino]ethoxy]ethoxy]acetyl]amino]ethylcarbamoyl]-2-[(2s,3s,4r,5s,6s)-3,4,5-trihydroxy-6-methyloxan-2- Chemical compound O[C@H]1[C@H](O)[C@H](O)[C@H](C)O[C@H]1O[C@H]1[C@H](O[C@H]2[C@@H]([C@@H](O[C@@H](CC3CCCCC3)C(O)=O)[C@@H](O)[C@@H](CO)O2)OC(=O)C=2C=CC=CC=2)C[C@H](C(=O)NCCNC(=O)COCCOCC(=O)NC=2C3=C(C=C(C=C3C=C(C=2)S(O)(=O)=O)S(O)(=O)=O)S(O)(=O)=O)C[C@@H]1NC(=O)C1=CC(=O)NC(=O)N1 VXBNTHRZPJLRSS-PTCSXESPSA-N 0.000 description 2
- NMSRALOLNIBERV-SYDPRGILSA-N (3as,6ar)-4,5,6,6a-tetrahydro-3ah-cyclopenta[c]furan-1,3-dione Chemical compound C1CC[C@@H]2C(=O)OC(=O)[C@@H]21 NMSRALOLNIBERV-SYDPRGILSA-N 0.000 description 2
- MUTGBJKUEZFXGO-OLQVQODUSA-N (3as,7ar)-3a,4,5,6,7,7a-hexahydro-2-benzofuran-1,3-dione Chemical compound C1CCC[C@@H]2C(=O)OC(=O)[C@@H]21 MUTGBJKUEZFXGO-OLQVQODUSA-N 0.000 description 2
- JHHZLHWJQPUNKB-SCSAIBSYSA-N (3r)-pyrrolidin-3-ol Chemical compound O[C@@H]1CCNC1 JHHZLHWJQPUNKB-SCSAIBSYSA-N 0.000 description 2
- ALZLTHLQMAFAPA-SCSAIBSYSA-N (4r)-4-methyloxolan-2-one Chemical compound C[C@H]1COC(=O)C1 ALZLTHLQMAFAPA-SCSAIBSYSA-N 0.000 description 2
- NVTAXTNNSSZOFU-UHFFFAOYSA-N (5-methyl-1,2-thiazol-3-yl)methanol Chemical compound CC1=CC(CO)=NS1 NVTAXTNNSSZOFU-UHFFFAOYSA-N 0.000 description 2
- WRADPCFZZWXOTI-BMRADRMJSA-N (9E)-10-nitrooctadecenoic acid Chemical compound CCCCCCCC\C([N+]([O-])=O)=C/CCCCCCCC(O)=O WRADPCFZZWXOTI-BMRADRMJSA-N 0.000 description 2
- UWYZHKAOTLEWKK-UHFFFAOYSA-N 1,2,3,4-tetrahydroisoquinoline Chemical compound C1=CC=C2CNCCC2=C1 UWYZHKAOTLEWKK-UHFFFAOYSA-N 0.000 description 2
- CTIOCGQJYWNIBA-UHFFFAOYSA-N 1,5-dimethyltriazole-4-carboxylic acid Chemical compound CC1=C(C(O)=O)N=NN1C CTIOCGQJYWNIBA-UHFFFAOYSA-N 0.000 description 2
- WQINSVOOIJDOLJ-UHFFFAOYSA-N 2-(1,3-dioxoisoindol-2-yl)acetic acid Chemical compound C1=CC=C2C(=O)N(CC(=O)O)C(=O)C2=C1 WQINSVOOIJDOLJ-UHFFFAOYSA-N 0.000 description 2
- WJBMRZAHTUFBGE-UHFFFAOYSA-N 2-(3-methoxyphenyl)ethanamine Chemical compound COC1=CC=CC(CCN)=C1 WJBMRZAHTUFBGE-UHFFFAOYSA-N 0.000 description 2
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 2
- KKAOOGUDSIHEGY-UHFFFAOYSA-N 3-(chloromethyl)-5-methyl-1,2-thiazole Chemical compound CC1=CC(CCl)=NS1 KKAOOGUDSIHEGY-UHFFFAOYSA-N 0.000 description 2
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 2
- OQHVVOYDDRBQRI-UHFFFAOYSA-N 4-(trifluoromethyl)pyrimidine-5-carboxylic acid Chemical compound OC(=O)C1=CN=CN=C1C(F)(F)F OQHVVOYDDRBQRI-UHFFFAOYSA-N 0.000 description 2
- NALVGTOMKSKFFV-UHFFFAOYSA-N 4-fluoro-3-methoxybenzaldehyde Chemical compound COC1=CC(C=O)=CC=C1F NALVGTOMKSKFFV-UHFFFAOYSA-N 0.000 description 2
- FJNCXZZQNBKEJT-UHFFFAOYSA-N 8beta-hydroxymarrubiin Natural products O1C(=O)C2(C)CCCC3(C)C2C1CC(C)(O)C3(O)CCC=1C=COC=1 FJNCXZZQNBKEJT-UHFFFAOYSA-N 0.000 description 2
- ZHGNHOOVYPHPNJ-UHFFFAOYSA-N Amigdalin Chemical compound FC(F)(F)C(=O)OCC1OC(OCC2OC(OC(C#N)C3=CC=CC=C3)C(OC(=O)C(F)(F)F)C(OC(=O)C(F)(F)F)C2OC(=O)C(F)(F)F)C(OC(=O)C(F)(F)F)C(OC(=O)C(F)(F)F)C1OC(=O)C(F)(F)F ZHGNHOOVYPHPNJ-UHFFFAOYSA-N 0.000 description 2
- 208000023275 Autoimmune disease Diseases 0.000 description 2
- TXGZJQLMVSIZEI-UQMAOPSPSA-N Bardoxolone Chemical compound C1=C(C#N)C(=O)C(C)(C)[C@@H]2CC[C@@]3(C)[C@]4(C)CC[C@@]5(C(O)=O)CCC(C)(C)C[C@H]5[C@H]4C(=O)C=C3[C@]21C TXGZJQLMVSIZEI-UQMAOPSPSA-N 0.000 description 2
- 206010055113 Breast cancer metastatic Diseases 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 2
- 208000024172 Cardiovascular disease Diseases 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
- LMHIPJMTZHDKEW-XQYLJSSYSA-M Epoprostenol sodium Chemical compound [Na+].O1\C(=C/CCCC([O-])=O)C[C@@H]2[C@@H](/C=C/[C@@H](O)CCCCC)[C@H](O)C[C@@H]21 LMHIPJMTZHDKEW-XQYLJSSYSA-M 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 102100021519 Hemoglobin subunit beta Human genes 0.000 description 2
- 108091005904 Hemoglobin subunit beta Proteins 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 2
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 2
- VQTUBCCKSQIDNK-UHFFFAOYSA-N Isobutene Chemical compound CC(C)=C VQTUBCCKSQIDNK-UHFFFAOYSA-N 0.000 description 2
- PWKSKIMOESPYIA-BYPYZUCNSA-N L-N-acetyl-Cysteine Chemical compound CC(=O)N[C@@H](CS)C(O)=O PWKSKIMOESPYIA-BYPYZUCNSA-N 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- 238000006751 Mitsunobu reaction Methods 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- 241000699660 Mus musculus Species 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 2
- LQZMLBORDGWNPD-UHFFFAOYSA-N N-iodosuccinimide Chemical compound IN1C(=O)CCC1=O LQZMLBORDGWNPD-UHFFFAOYSA-N 0.000 description 2
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
- YNPNZTXNASCQKK-UHFFFAOYSA-N Phenanthrene Natural products C1=CC=C2C3=CC=CC=C3C=CC2=C1 YNPNZTXNASCQKK-UHFFFAOYSA-N 0.000 description 2
- 229940123932 Phosphodiesterase 4 inhibitor Drugs 0.000 description 2
- 102000004861 Phosphoric Diester Hydrolases Human genes 0.000 description 2
- 108090001050 Phosphoric Diester Hydrolases Proteins 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- 206010038687 Respiratory distress Diseases 0.000 description 2
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical class [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- NHUHCSRWZMLRLA-UHFFFAOYSA-N Sulfisoxazole Chemical compound CC1=NOC(NS(=O)(=O)C=2C=CC(N)=CC=2)=C1C NHUHCSRWZMLRLA-UHFFFAOYSA-N 0.000 description 2
- 241000282485 Vulpes vulpes Species 0.000 description 2
- CTTCMOQCBQCIAO-SECBINFHSA-N [(3R)-1-(5-methylpyridazin-3-yl)pyrrolidin-3-yl] methanesulfonate Chemical compound CS(=O)(=O)O[C@H]1CN(CC1)C=1N=NC=C(C=1)C CTTCMOQCBQCIAO-SECBINFHSA-N 0.000 description 2
- DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 description 2
- 229960004308 acetylcysteine Drugs 0.000 description 2
- ASMXXROZKSBQIH-VITNCHFBSA-N aclidinium Chemical compound C([C@@H](C(CC1)CC2)OC(=O)C(O)(C=3SC=CC=3)C=3SC=CC=3)[N+]21CCCOC1=CC=CC=C1 ASMXXROZKSBQIH-VITNCHFBSA-N 0.000 description 2
- OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 description 2
- 230000032683 aging Effects 0.000 description 2
- 239000000556 agonist Substances 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 229910000272 alkali metal oxide Inorganic materials 0.000 description 2
- 150000001350 alkyl halides Chemical class 0.000 description 2
- 230000029936 alkylation Effects 0.000 description 2
- 238000005804 alkylation reaction Methods 0.000 description 2
- OUJTZYPIHDYQMC-LJQANCHMSA-N ambrisentan Chemical compound O([C@@H](C(OC)(C=1C=CC=CC=1)C=1C=CC=CC=1)C(O)=O)C1=NC(C)=CC(C)=N1 OUJTZYPIHDYQMC-LJQANCHMSA-N 0.000 description 2
- 150000001409 amidines Chemical class 0.000 description 2
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 description 2
- 235000019270 ammonium chloride Nutrition 0.000 description 2
- 150000003863 ammonium salts Chemical class 0.000 description 2
- 229940121363 anti-inflammatory agent Drugs 0.000 description 2
- 239000002260 anti-inflammatory agent Substances 0.000 description 2
- 230000006851 antioxidant defense Effects 0.000 description 2
- 230000003078 antioxidant effect Effects 0.000 description 2
- 230000006907 apoptotic process Effects 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 239000012300 argon atmosphere Substances 0.000 description 2
- 125000003435 aroyl group Chemical group 0.000 description 2
- 206010003246 arthritis Diseases 0.000 description 2
- 125000005101 aryl methoxy carbonyl group Chemical group 0.000 description 2
- 210000001130 astrocyte Anatomy 0.000 description 2
- 125000002393 azetidinyl group Chemical group 0.000 description 2
- 230000004888 barrier function Effects 0.000 description 2
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 2
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 2
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 2
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 2
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 2
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 2
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 2
- 125000002618 bicyclic heterocycle group Chemical group 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- GJPICJJJRGTNOD-UHFFFAOYSA-N bosentan Chemical compound COC1=CC=CC=C1OC(C(=NC(=N1)C=2N=CC=CN=2)OCCO)=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 GJPICJJJRGTNOD-UHFFFAOYSA-N 0.000 description 2
- 208000029028 brain injury Diseases 0.000 description 2
- 125000002843 carboxylic acid group Chemical group 0.000 description 2
- 230000007211 cardiovascular event Effects 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 150000001805 chlorine compounds Chemical class 0.000 description 2
- 125000003016 chromanyl group Chemical group O1C(CCC2=CC=CC=C12)* 0.000 description 2
- 208000018631 connective tissue disease Diseases 0.000 description 2
- 201000004180 corneal endothelial dystrophy Diseases 0.000 description 2
- 230000000875 corresponding effect Effects 0.000 description 2
- 239000013058 crude material Substances 0.000 description 2
- 150000004292 cyclic ethers Chemical class 0.000 description 2
- 125000002993 cycloalkylene group Chemical group 0.000 description 2
- NXQGGXCHGDYOHB-UHFFFAOYSA-L cyclopenta-1,4-dien-1-yl(diphenyl)phosphane;dichloropalladium;iron(2+) Chemical compound [Fe+2].Cl[Pd]Cl.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 NXQGGXCHGDYOHB-UHFFFAOYSA-L 0.000 description 2
- CIISBNCSMVCNIP-UHFFFAOYSA-N cyclopentane-1,2-dione Chemical class O=C1CCCC1=O CIISBNCSMVCNIP-UHFFFAOYSA-N 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 235000005911 diet Nutrition 0.000 description 2
- 230000037213 diet Effects 0.000 description 2
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 2
- 125000005048 dihydroisoxazolyl group Chemical group O1N(CC=C1)* 0.000 description 2
- 125000004655 dihydropyridinyl group Chemical group N1(CC=CC=C1)* 0.000 description 2
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
- 238000009510 drug design Methods 0.000 description 2
- 230000004064 dysfunction Effects 0.000 description 2
- 230000002526 effect on cardiovascular system Effects 0.000 description 2
- 150000002085 enols Chemical class 0.000 description 2
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 2
- YMZOFGFFLQIGPI-UHFFFAOYSA-N ethyl 4-(difluoromethyl)pyrimidine-5-carboxylate Chemical compound CCOC(=O)C1=CN=CN=C1C(F)F YMZOFGFFLQIGPI-UHFFFAOYSA-N 0.000 description 2
- LIWAQLJGPBVORC-UHFFFAOYSA-N ethylmethylamine Chemical compound CCNC LIWAQLJGPBVORC-UHFFFAOYSA-N 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- NKHAVTQWNUWKEO-UHFFFAOYSA-N fumaric acid monomethyl ester Natural products COC(=O)C=CC(O)=O NKHAVTQWNUWKEO-UHFFFAOYSA-N 0.000 description 2
- 125000002541 furyl group Chemical group 0.000 description 2
- 150000003278 haem Chemical class 0.000 description 2
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 2
- 231100000844 hepatocellular carcinoma Toxicity 0.000 description 2
- 238000007327 hydrogenolysis reaction Methods 0.000 description 2
- HIFJCPQKFCZDDL-ACWOEMLNSA-N iloprost Chemical compound C1\C(=C/CCCC(O)=O)C[C@@H]2[C@@H](/C=C/[C@@H](O)C(C)CC#CC)[C@H](O)C[C@@H]21 HIFJCPQKFCZDDL-ACWOEMLNSA-N 0.000 description 2
- 125000002883 imidazolyl group Chemical group 0.000 description 2
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 2
- JYGFTBXVXVMTGB-UHFFFAOYSA-N indolin-2-one Chemical compound C1=CC=C2NC(=O)CC2=C1 JYGFTBXVXVMTGB-UHFFFAOYSA-N 0.000 description 2
- 125000001041 indolyl group Chemical group 0.000 description 2
- 230000002757 inflammatory effect Effects 0.000 description 2
- 230000000977 initiatory effect Effects 0.000 description 2
- 238000009434 installation Methods 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- UEXQBEVWFZKHNB-UHFFFAOYSA-N intermediate 29 Natural products C1=CC(N)=CC=C1NC1=NC=CC=N1 UEXQBEVWFZKHNB-UHFFFAOYSA-N 0.000 description 2
- 210000002490 intestinal epithelial cell Anatomy 0.000 description 2
- 125000004594 isoindolinyl group Chemical group C1(NCC2=CC=CC=C12)* 0.000 description 2
- 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 description 2
- 125000001786 isothiazolyl group Chemical group 0.000 description 2
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- 210000004072 lung Anatomy 0.000 description 2
- 230000014759 maintenance of location Effects 0.000 description 2
- 230000004060 metabolic process Effects 0.000 description 2
- GQJCAQADCPTHKN-UHFFFAOYSA-N methyl 2,2-difluoro-2-fluorosulfonylacetate Chemical compound COC(=O)C(F)(F)S(F)(=O)=O GQJCAQADCPTHKN-UHFFFAOYSA-N 0.000 description 2
- MRQXTYSTUICYRR-UHFFFAOYSA-N methyl 2-(2,3,4-trifluorophenyl)acetate Chemical compound COC(=O)CC1=CC=C(F)C(F)=C1F MRQXTYSTUICYRR-UHFFFAOYSA-N 0.000 description 2
- ORAKNQSHWMHCEY-UHFFFAOYSA-N methyl 2-pyridin-2-ylacetate Chemical compound COC(=O)CC1=CC=CC=N1 ORAKNQSHWMHCEY-UHFFFAOYSA-N 0.000 description 2
- MVHHQOCEOUNTID-UHFFFAOYSA-N methyl 5-methyl-1,2-oxazole-3-carboxylate Chemical compound COC(=O)C=1C=C(C)ON=1 MVHHQOCEOUNTID-UHFFFAOYSA-N 0.000 description 2
- GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical group [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 description 2
- 210000000274 microglia Anatomy 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- NKHAVTQWNUWKEO-NSCUHMNNSA-N monomethyl fumarate Chemical compound COC(=O)\C=C\C(O)=O NKHAVTQWNUWKEO-NSCUHMNNSA-N 0.000 description 2
- 229940005650 monomethyl fumarate Drugs 0.000 description 2
- 125000001064 morpholinomethyl group Chemical group [H]C([H])(*)N1C([H])([H])C([H])([H])OC([H])([H])C1([H])[H] 0.000 description 2
- 230000035772 mutation Effects 0.000 description 2
- NTMHWRHEGDRTPD-UHFFFAOYSA-N n-(4-azidosulfonylphenyl)acetamide Chemical compound CC(=O)NC1=CC=C(S(=O)(=O)N=[N+]=[N-])C=C1 NTMHWRHEGDRTPD-UHFFFAOYSA-N 0.000 description 2
- RJCWBNBKOKFWNY-IDPLTSGASA-N n-[(4as,6ar,6bs,8ar,12as,14ar,14bs)-11-cyano-2,2,6a,6b,9,9,12a-heptamethyl-10,14-dioxo-1,3,4,5,6,7,8,8a,14a,14b-decahydropicen-4a-yl]-2,2-difluoropropanamide Chemical compound C([C@@]12C)=C(C#N)C(=O)C(C)(C)[C@@H]1CC[C@]1(C)C2=CC(=O)[C@@H]2[C@@H]3CC(C)(C)CC[C@]3(NC(=O)C(F)(F)C)CC[C@]21C RJCWBNBKOKFWNY-IDPLTSGASA-N 0.000 description 2
- 125000001624 naphthyl group Chemical group 0.000 description 2
- 125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 description 2
- 230000007971 neurological deficit Effects 0.000 description 2
- WPHGSKGZRAQSGP-UHFFFAOYSA-N norcarane Chemical compound C1CCCC2CC21 WPHGSKGZRAQSGP-UHFFFAOYSA-N 0.000 description 2
- 125000001715 oxadiazolyl group Chemical group 0.000 description 2
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
- 239000007800 oxidant agent Substances 0.000 description 2
- 239000006072 paste Substances 0.000 description 2
- 230000008506 pathogenesis Effects 0.000 description 2
- 239000002587 phosphodiesterase IV inhibitor Substances 0.000 description 2
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 2
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
- HYAFETHFCAUJAY-UHFFFAOYSA-N pioglitazone Chemical compound N1=CC(CC)=CC=C1CCOC(C=C1)=CC=C1CC1C(=O)NC(=O)S1 HYAFETHFCAUJAY-UHFFFAOYSA-N 0.000 description 2
- 125000004193 piperazinyl group Chemical group 0.000 description 2
- 125000003367 polycyclic group Chemical group 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- 229960005205 prednisolone Drugs 0.000 description 2
- 238000002953 preparative HPLC Methods 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- 230000000069 prophylactic effect Effects 0.000 description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 230000004850 protein–protein interaction Effects 0.000 description 2
- 125000001042 pteridinyl group Chemical group N1=C(N=CC2=NC=CN=C12)* 0.000 description 2
- 230000002685 pulmonary effect Effects 0.000 description 2
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 2
- 125000003373 pyrazinyl group Chemical group 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 125000000168 pyrrolyl group Chemical group 0.000 description 2
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 2
- 150000003254 radicals Chemical class 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 230000010410 reperfusion Effects 0.000 description 2
- 230000002441 reversible effect Effects 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 description 2
- 241000894007 species Species 0.000 description 2
- 125000003003 spiro group Chemical group 0.000 description 2
- 239000012258 stirred mixture Substances 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- 230000001629 suppression Effects 0.000 description 2
- 208000011580 syndromic disease Diseases 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 230000009885 systemic effect Effects 0.000 description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- HJUGFYREWKUQJT-UHFFFAOYSA-N tetrabromomethane Chemical compound BrC(Br)(Br)Br HJUGFYREWKUQJT-UHFFFAOYSA-N 0.000 description 2
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 2
- 150000003536 tetrazoles Chemical class 0.000 description 2
- ZFXYFBGIUFBOJW-UHFFFAOYSA-N theophylline Chemical compound O=C1N(C)C(=O)N(C)C2=C1NC=N2 ZFXYFBGIUFBOJW-UHFFFAOYSA-N 0.000 description 2
- 125000000335 thiazolyl group Chemical group 0.000 description 2
- 125000001544 thienyl group Chemical group 0.000 description 2
- 230000000699 topical effect Effects 0.000 description 2
- 238000011830 transgenic mouse model Methods 0.000 description 2
- 229960005032 treprostinil Drugs 0.000 description 2
- 125000001425 triazolyl group Chemical group 0.000 description 2
- IMNIMPAHZVJRPE-UHFFFAOYSA-N triethylenediamine Chemical compound C1CN2CCN1CC2 IMNIMPAHZVJRPE-UHFFFAOYSA-N 0.000 description 2
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 2
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
- CSRZQMIRAZTJOY-UHFFFAOYSA-N trimethylsilyl iodide Chemical compound C[Si](C)(C)I CSRZQMIRAZTJOY-UHFFFAOYSA-N 0.000 description 2
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
- 238000000825 ultraviolet detection Methods 0.000 description 2
- 230000003827 upregulation Effects 0.000 description 2
- 239000011701 zinc Substances 0.000 description 2
- XWTYSIMOBUGWOL-UHFFFAOYSA-N (+-)-Terbutaline Chemical compound CC(C)(C)NCC(O)C1=CC(O)=CC(O)=C1 XWTYSIMOBUGWOL-UHFFFAOYSA-N 0.000 description 1
- XUFXOAAUWZOOIT-SXARVLRPSA-N (2R,3R,4R,5S,6R)-5-[[(2R,3R,4R,5S,6R)-5-[[(2R,3R,4S,5S,6R)-3,4-dihydroxy-6-methyl-5-[[(1S,4R,5S,6S)-4,5,6-trihydroxy-3-(hydroxymethyl)-1-cyclohex-2-enyl]amino]-2-oxanyl]oxy]-3,4-dihydroxy-6-(hydroxymethyl)-2-oxanyl]oxy]-6-(hydroxymethyl)oxane-2,3,4-triol Chemical compound O([C@H]1O[C@H](CO)[C@H]([C@@H]([C@H]1O)O)O[C@H]1O[C@@H]([C@H]([C@H](O)[C@H]1O)N[C@@H]1[C@@H]([C@@H](O)[C@H](O)C(CO)=C1)O)C)[C@@H]1[C@@H](CO)O[C@@H](O)[C@H](O)[C@H]1O XUFXOAAUWZOOIT-SXARVLRPSA-N 0.000 description 1
- ROFSJMGFGWMMGQ-UHFFFAOYSA-N (5,5-dimethyl-4H-1,2-oxazol-3-yl)methanol Chemical compound CC1(CC(=NO1)CO)C ROFSJMGFGWMMGQ-UHFFFAOYSA-N 0.000 description 1
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 description 1
- XLYMOEINVGRTEX-ONEGZZNKSA-N (e)-4-ethoxy-4-oxobut-2-enoic acid Chemical class CCOC(=O)\C=C\C(O)=O XLYMOEINVGRTEX-ONEGZZNKSA-N 0.000 description 1
- 125000003363 1,3,5-triazinyl group Chemical group N1=C(N=CN=C1)* 0.000 description 1
- NDZYPHLNJZSQJY-QNWVGRARSA-N 1-(5-acetyl-4-methyl-1,3-thiazol-2-yl)-3-[(1r,2s)-2-[[(3s)-3-[(4-fluorophenyl)methyl]piperidin-1-yl]methyl]cyclohexyl]urea Chemical compound CC1=C(C(=O)C)SC(NC(=O)N[C@H]2[C@@H](CCCC2)CN2C[C@H](CC=3C=CC(F)=CC=3)CCC2)=N1 NDZYPHLNJZSQJY-QNWVGRARSA-N 0.000 description 1
- NHMIZLSLXVYTTL-UHFFFAOYSA-N 1-[3-amino-5-(hydroxymethyl)phenyl]-2-[1-(4-methoxyphenyl)propan-2-ylamino]ethanol Chemical compound C1=CC(OC)=CC=C1CC(C)NCC(O)C1=CC(N)=CC(CO)=C1 NHMIZLSLXVYTTL-UHFFFAOYSA-N 0.000 description 1
- CDQVVPUXSPZONN-WPPLYIOHSA-N 1-[6-amino-9-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]purin-2-yl]-n-methylpyrazole-4-carboxamide;hydrate Chemical compound O.C1=C(C(=O)NC)C=NN1C1=NC(N)=C(N=CN2[C@H]3[C@@H]([C@H](O)[C@@H](CO)O3)O)C2=N1 CDQVVPUXSPZONN-WPPLYIOHSA-N 0.000 description 1
- XPUICTAIJXJSFY-SNAWJCMRSA-N 1-fluoro-2-methoxy-4-[(E)-2-nitroethenyl]benzene Chemical compound COC1=CC(\C=C\[N+]([O-])=O)=CC=C1F XPUICTAIJXJSFY-SNAWJCMRSA-N 0.000 description 1
- 125000004343 1-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C([H])([H])[H] 0.000 description 1
- PDNHLCRMUIGNBV-UHFFFAOYSA-N 1-pyridin-2-ylethanamine Chemical compound CC(N)C1=CC=CC=N1 PDNHLCRMUIGNBV-UHFFFAOYSA-N 0.000 description 1
- XWIYUCRMWCHYJR-UHFFFAOYSA-N 1h-pyrrolo[3,2-b]pyridine Chemical compound C1=CC=C2NC=CC2=N1 XWIYUCRMWCHYJR-UHFFFAOYSA-N 0.000 description 1
- 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 1
- GBBSAMQTQCPOBF-UHFFFAOYSA-N 2,4,6-trimethyl-1,3,5,2,4,6-trioxatriborinane Chemical group CB1OB(C)OB(C)O1 GBBSAMQTQCPOBF-UHFFFAOYSA-N 0.000 description 1
- SYOANZBNGDEJFH-UHFFFAOYSA-N 2,5-dihydro-1h-triazole Chemical compound C1NNN=C1 SYOANZBNGDEJFH-UHFFFAOYSA-N 0.000 description 1
- FSGDZRKNLLCBDV-UHFFFAOYSA-N 2-(4-fluoro-3-methoxyphenyl)ethanamine Chemical compound COC1=CC(CCN)=CC=C1F FSGDZRKNLLCBDV-UHFFFAOYSA-N 0.000 description 1
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
- KZSKGLFYQAYZCO-UHFFFAOYSA-N 2-[3-[2-chloro-4-[[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy]phenyl]-3-hydroxyazetidin-1-yl]pyridine-4-carboxylic acid Chemical compound OC(=O)C1=CC=NC(N2CC(O)(C2)C=2C(=CC(OCC=3C(=NOC=3C3CC3)C=3C(=CC=CC=3Cl)Cl)=CC=2)Cl)=C1 KZSKGLFYQAYZCO-UHFFFAOYSA-N 0.000 description 1
- XKTLIZATQZBDGG-CQSZACIVSA-N 2-[[(1S)-5-chloro-8-hydroxy-1,2,3,4-tetrahydroisoquinolin-1-yl]methyl]isoindole-1,3-dione Chemical compound ClC1=C2CCN[C@@H](C2=C(C=C1)O)CN1C(C2=CC=CC=C2C1=O)=O XKTLIZATQZBDGG-CQSZACIVSA-N 0.000 description 1
- KWSIQJUNYMMCTB-UHFFFAOYSA-N 2-[[4-[carboxymethyl-(4-methoxyphenyl)sulfonylamino]naphthalen-1-yl]-(4-methoxyphenyl)sulfonylamino]acetic acid Chemical compound C1=CC(OC)=CC=C1S(=O)(=O)N(CC(O)=O)C(C1=CC=CC=C11)=CC=C1N(CC(O)=O)S(=O)(=O)C1=CC=C(OC)C=C1 KWSIQJUNYMMCTB-UHFFFAOYSA-N 0.000 description 1
- BWPGCNBJSRYYLD-UHFFFAOYSA-N 2-diazonio-1,4-dimethoxy-3-oxobut-1-en-1-olate Chemical compound COCC(=O)C(=[N+]=[N-])C(=O)OC BWPGCNBJSRYYLD-UHFFFAOYSA-N 0.000 description 1
- FWCVZAQENIZVMY-UHFFFAOYSA-N 2-hydroxy-6-[[2-(2-propan-2-ylpyrazol-3-yl)pyridin-3-yl]methoxy]benzaldehyde Chemical compound CC(C)N1N=CC=C1C1=NC=CC=C1COC1=CC=CC(O)=C1C=O FWCVZAQENIZVMY-UHFFFAOYSA-N 0.000 description 1
- APOYTRAZFJURPB-UHFFFAOYSA-N 2-methoxy-n-(2-methoxyethyl)-n-(trifluoro-$l^{4}-sulfanyl)ethanamine Chemical compound COCCN(S(F)(F)F)CCOC APOYTRAZFJURPB-UHFFFAOYSA-N 0.000 description 1
- ASUDFOJKTJLAIK-UHFFFAOYSA-N 2-methoxyethanamine Chemical compound COCCN ASUDFOJKTJLAIK-UHFFFAOYSA-N 0.000 description 1
- 125000004637 2-oxopiperidinyl group Chemical group O=C1N(CCCC1)* 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- XOBXSZMVFDYRBL-UHFFFAOYSA-N 4,5,6,7-tetrahydrotriazolo[1,5-a]pyridin-3-ylmethanol Chemical compound C1CCCC2=C(CO)N=NN21 XOBXSZMVFDYRBL-UHFFFAOYSA-N 0.000 description 1
- FHVANDNMPXZWKJ-UHFFFAOYSA-N 4-(difluoromethyl)pyrimidine-5-carboxylic acid Chemical compound OC(=O)C1=CN=CN=C1C(F)F FHVANDNMPXZWKJ-UHFFFAOYSA-N 0.000 description 1
- SWLAMJPTOQZTAE-UHFFFAOYSA-N 4-[2-[(5-chloro-2-methoxybenzoyl)amino]ethyl]benzoic acid Chemical class COC1=CC=C(Cl)C=C1C(=O)NCCC1=CC=C(C(O)=O)C=C1 SWLAMJPTOQZTAE-UHFFFAOYSA-N 0.000 description 1
- BMMHZTIQZODVHZ-UHFFFAOYSA-N 4-[2-[[2-[3-amino-5-(hydroxymethyl)phenyl]-2-hydroxyethyl]amino]propyl]phenol Chemical compound C=1C(N)=CC(CO)=CC=1C(O)CNC(C)CC1=CC=C(O)C=C1 BMMHZTIQZODVHZ-UHFFFAOYSA-N 0.000 description 1
- ZLBQDMQNBKRMOW-UHFFFAOYSA-N 4-iodo-3-(methoxymethyl)-5-methyl-1,2-oxazole Chemical compound COCC1=NOC(C)=C1I ZLBQDMQNBKRMOW-UHFFFAOYSA-N 0.000 description 1
- CNPURSDMOWDNOQ-UHFFFAOYSA-N 4-methoxy-7h-pyrrolo[2,3-d]pyrimidin-2-amine Chemical compound COC1=NC(N)=NC2=C1C=CN2 CNPURSDMOWDNOQ-UHFFFAOYSA-N 0.000 description 1
- KZAQTVQJVOALDK-UHFFFAOYSA-N 5-(trifluoromethyl)-1h-1,2,4-triazole Chemical compound FC(F)(F)C=1N=CNN=1 KZAQTVQJVOALDK-UHFFFAOYSA-N 0.000 description 1
- LSLYOANBFKQKPT-DIFFPNOSSA-N 5-[(1r)-1-hydroxy-2-[[(2r)-1-(4-hydroxyphenyl)propan-2-yl]amino]ethyl]benzene-1,3-diol Chemical compound C([C@@H](C)NC[C@H](O)C=1C=C(O)C=C(O)C=1)C1=CC=C(O)C=C1 LSLYOANBFKQKPT-DIFFPNOSSA-N 0.000 description 1
- IHOXNOQMRZISPV-YJYMSZOUSA-N 5-[(1r)-1-hydroxy-2-[[(2r)-1-(4-methoxyphenyl)propan-2-yl]azaniumyl]ethyl]-2-oxo-1h-quinolin-8-olate Chemical compound C1=CC(OC)=CC=C1C[C@@H](C)NC[C@H](O)C1=CC=C(O)C2=C1C=CC(=O)N2 IHOXNOQMRZISPV-YJYMSZOUSA-N 0.000 description 1
- PXRKCOCTEMYUEG-UHFFFAOYSA-N 5-aminoisoindole-1,3-dione Chemical compound NC1=CC=C2C(=O)NC(=O)C2=C1 PXRKCOCTEMYUEG-UHFFFAOYSA-N 0.000 description 1
- QRXMUCSWCMTJGU-UHFFFAOYSA-N 5-bromo-4-chloro-3-indolyl phosphate Chemical compound C1=C(Br)C(Cl)=C2C(OP(O)(=O)O)=CNC2=C1 QRXMUCSWCMTJGU-UHFFFAOYSA-N 0.000 description 1
- GWGNPYYVGANHRJ-GDBMZVCRSA-N 6-[(3S,4S)-4-methyl-1-(pyrimidin-2-ylmethyl)pyrrolidin-3-yl]-3-(oxan-4-yl)-7H-imidazo[1,5-a]pyrazin-8-one Chemical compound C[C@H]1[C@@H](CN(C1)CC1=NC=CC=N1)C=1NC(C=2N(C=1)C(=NC=2)C1CCOCC1)=O GWGNPYYVGANHRJ-GDBMZVCRSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 238000013296 A/J mouse Methods 0.000 description 1
- 102000007469 Actins Human genes 0.000 description 1
- 108010085238 Actins Proteins 0.000 description 1
- 229940077274 Alpha glucosidase inhibitor Drugs 0.000 description 1
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 1
- 239000005695 Ammonium acetate Substances 0.000 description 1
- 229920000856 Amylose Polymers 0.000 description 1
- 108091023037 Aptamer Proteins 0.000 description 1
- 229910015845 BBr3 Inorganic materials 0.000 description 1
- 102100039705 Beta-2 adrenergic receptor Human genes 0.000 description 1
- 229940123208 Biguanide Drugs 0.000 description 1
- 201000004569 Blindness Diseases 0.000 description 1
- VOVIALXJUBGFJZ-KWVAZRHASA-N Budesonide Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@@H]2[C@@H]1[C@@H]1C[C@H]3OC(CCC)O[C@@]3(C(=O)CO)[C@@]1(C)C[C@@H]2O VOVIALXJUBGFJZ-KWVAZRHASA-N 0.000 description 1
- 239000002126 C01EB10 - Adenosine Substances 0.000 description 1
- QGBIFMJAQARMNQ-QISPFCDLSA-N C1([C@@H](F)C2)=CC(=O)CC[C@]1(C)[C@]1(F)[C@@H]2[C@@H]2C[C@H]3O[C@@H](CCC)O[C@@]3(SC)[C@@]2(C)C[C@@H]1O Chemical compound C1([C@@H](F)C2)=CC(=O)CC[C@]1(C)[C@]1(F)[C@@H]2[C@@H]2C[C@H]3O[C@@H](CCC)O[C@@]3(SC)[C@@]2(C)C[C@@H]1O QGBIFMJAQARMNQ-QISPFCDLSA-N 0.000 description 1
- JSTUHDJWVGZIJR-UHFFFAOYSA-N C12=C(N=NN2CCOC1)CO Chemical compound C12=C(N=NN2CCOC1)CO JSTUHDJWVGZIJR-UHFFFAOYSA-N 0.000 description 1
- 108010059108 CD18 Antigens Proteins 0.000 description 1
- ARSIOSQVJQFAAK-UHFFFAOYSA-N CN1C=NC2=C1N=C(C=C2)CO Chemical compound CN1C=NC2=C1N=C(C=C2)CO ARSIOSQVJQFAAK-UHFFFAOYSA-N 0.000 description 1
- FDJOOADUEJFPAX-UHFFFAOYSA-N COC(=O)c1ccc2ncn(C)c2n1 Chemical compound COC(=O)c1ccc2ncn(C)c2n1 FDJOOADUEJFPAX-UHFFFAOYSA-N 0.000 description 1
- WWRHUNWXRFROBC-UHFFFAOYSA-N COC(C1=C(COCC2)N2N=N1)=O Chemical compound COC(C1=C(COCC2)N2N=N1)=O WWRHUNWXRFROBC-UHFFFAOYSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 108010077544 Chromatin Proteins 0.000 description 1
- LUKZNWIVRBCLON-GXOBDPJESA-N Ciclesonide Chemical compound C1([C@H]2O[C@@]3([C@H](O2)C[C@@H]2[C@@]3(C[C@H](O)[C@@H]3[C@@]4(C)C=CC(=O)C=C4CC[C@H]32)C)C(=O)COC(=O)C(C)C)CCCCC1 LUKZNWIVRBCLON-GXOBDPJESA-N 0.000 description 1
- XBUXXJUEBFDQHD-NHCUHLMSSA-N ClC1=C(C=CC(=C1)OCC=1C(=NOC1C1CC1)C1=C(C=CC=C1Cl)Cl)[C@@H]1[C@H](C1)C1=CC=C(C(=O)O)C=C1 Chemical compound ClC1=C(C=CC(=C1)OCC=1C(=NOC1C1CC1)C1=C(C=CC=C1Cl)Cl)[C@@H]1[C@H](C1)C1=CC=C(C(=O)O)C=C1 XBUXXJUEBFDQHD-NHCUHLMSSA-N 0.000 description 1
- 208000018458 Colitis-Associated Neoplasms Diseases 0.000 description 1
- 102000004266 Collagen Type IV Human genes 0.000 description 1
- 108010042086 Collagen Type IV Proteins 0.000 description 1
- 208000032170 Congenital Abnormalities Diseases 0.000 description 1
- 229910021595 Copper(I) iodide Inorganic materials 0.000 description 1
- 229920000858 Cyclodextrin Polymers 0.000 description 1
- 102100035429 Cystathionine gamma-lyase Human genes 0.000 description 1
- 239000012623 DNA damaging agent Substances 0.000 description 1
- JVHXJTBJCFBINQ-ADAARDCZSA-N Dapagliflozin Chemical compound C1=CC(OCC)=CC=C1CC1=CC([C@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)O)=CC=C1Cl JVHXJTBJCFBINQ-ADAARDCZSA-N 0.000 description 1
- 101100135868 Dictyostelium discoideum pde3 gene Proteins 0.000 description 1
- 241001649081 Dina Species 0.000 description 1
- 229940124213 Dipeptidyl peptidase 4 (DPP IV) inhibitor Drugs 0.000 description 1
- 206010061818 Disease progression Diseases 0.000 description 1
- 239000001692 EU approved anti-caking agent Substances 0.000 description 1
- 241000792859 Enema Species 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
- 239000005977 Ethylene Substances 0.000 description 1
- HTQBXNHDCUEHJF-XWLPCZSASA-N Exenatide Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(=O)NCC(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CO)C(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 HTQBXNHDCUEHJF-XWLPCZSASA-N 0.000 description 1
- 108010011459 Exenatide Proteins 0.000 description 1
- ZSSYTCQJKJZMPW-UHFFFAOYSA-N FC(C=1C(=NOC=1C)C(=O)OC)F Chemical compound FC(C=1C(=NOC=1C)C(=O)OC)F ZSSYTCQJKJZMPW-UHFFFAOYSA-N 0.000 description 1
- CKZJNFOXVWSNJB-UHFFFAOYSA-N FC(F)c1ncncc1CCl Chemical compound FC(F)c1ncncc1CCl CKZJNFOXVWSNJB-UHFFFAOYSA-N 0.000 description 1
- 208000004930 Fatty Liver Diseases 0.000 description 1
- 108010044495 Fetal Hemoglobin Proteins 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- DTHNMHAUYICORS-KTKZVXAJSA-N Glucagon-like peptide 1 Chemical class C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1N=CNC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 DTHNMHAUYICORS-KTKZVXAJSA-N 0.000 description 1
- FAEKWTJYAYMJKF-QHCPKHFHSA-N GlucoNorm Chemical compound C1=C(C(O)=O)C(OCC)=CC(CC(=O)N[C@@H](CC(C)C)C=2C(=CC=CC=2)N2CCCCC2)=C1 FAEKWTJYAYMJKF-QHCPKHFHSA-N 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 206010018910 Haemolysis Diseases 0.000 description 1
- 208000013875 Heart injury Diseases 0.000 description 1
- 102000002737 Heme Oxygenase-1 Human genes 0.000 description 1
- 108091005886 Hemoglobin subunit gamma Proteins 0.000 description 1
- 102100038617 Hemoglobin subunit gamma-2 Human genes 0.000 description 1
- 108010054147 Hemoglobins Proteins 0.000 description 1
- 102000001554 Hemoglobins Human genes 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101001018196 Homo sapiens Mitogen-activated protein kinase kinase kinase 5 Proteins 0.000 description 1
- VSNHCAURESNICA-UHFFFAOYSA-N Hydroxyurea Chemical compound NC(=O)NO VSNHCAURESNICA-UHFFFAOYSA-N 0.000 description 1
- 206010020880 Hypertrophy Diseases 0.000 description 1
- 229940126040 IMR-687 Drugs 0.000 description 1
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 1
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 1
- 102000004877 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 229940122245 Janus kinase inhibitor Drugs 0.000 description 1
- 206010023203 Joint destruction Diseases 0.000 description 1
- 244000162475 Juniperus rigida Species 0.000 description 1
- 229930194542 Keto Natural products 0.000 description 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
- 229930182816 L-glutamine Natural products 0.000 description 1
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
- 229910010082 LiAlH Inorganic materials 0.000 description 1
- 239000000867 Lipoxygenase Inhibitor Substances 0.000 description 1
- YSDQQAXHVYUZIW-QCIJIYAXSA-N Liraglutide Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCNC(=O)CC[C@H](NC(=O)CCCCCCCCCCCCCCC)C(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=C(O)C=C1 YSDQQAXHVYUZIW-QCIJIYAXSA-N 0.000 description 1
- 108010019598 Liraglutide Proteins 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 239000012448 Lithium borohydride Substances 0.000 description 1
- 241000530268 Lycaena heteronea Species 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 1
- QXKHYNVANLEOEG-UHFFFAOYSA-N Methoxsalen Chemical group C1=CC(=O)OC2=C1C=C1C=COC1=C2OC QXKHYNVANLEOEG-UHFFFAOYSA-N 0.000 description 1
- 102100033127 Mitogen-activated protein kinase kinase kinase 5 Human genes 0.000 description 1
- UCHDWCPVSPXUMX-TZIWLTJVSA-N Montelukast Chemical compound CC(C)(O)C1=CC=CC=C1CC[C@H](C=1C=C(\C=C\C=2N=C3C=C(Cl)C=CC3=CC=2)C=CC=1)SCC1(CC(O)=O)CC1 UCHDWCPVSPXUMX-TZIWLTJVSA-N 0.000 description 1
- 102000014415 Muscarinic acetylcholine receptor Human genes 0.000 description 1
- 108050003473 Muscarinic acetylcholine receptor Proteins 0.000 description 1
- 229940121948 Muscarinic receptor antagonist Drugs 0.000 description 1
- 108010021466 Mutant Proteins Proteins 0.000 description 1
- 102000008300 Mutant Proteins Human genes 0.000 description 1
- 208000036110 Neuroinflammatory disease Diseases 0.000 description 1
- 102100029438 Nitric oxide synthase, inducible Human genes 0.000 description 1
- 101710089543 Nitric oxide synthase, inducible Proteins 0.000 description 1
- 101710114687 Nuclear factor erythroid 2-related factor 2 Proteins 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- 102000008212 P-Selectin Human genes 0.000 description 1
- 108010035766 P-Selectin Proteins 0.000 description 1
- 229940076380 PDE9 inhibitor Drugs 0.000 description 1
- 239000012828 PI3K inhibitor Substances 0.000 description 1
- 101150014691 PPARA gene Proteins 0.000 description 1
- 208000037273 Pathologic Processes Diseases 0.000 description 1
- NFHFRUOZVGFOOS-UHFFFAOYSA-N Pd(PPh3)4 Substances [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 1
- SCKXCAADGDQQCS-UHFFFAOYSA-N Performic acid Chemical compound OOC=O SCKXCAADGDQQCS-UHFFFAOYSA-N 0.000 description 1
- 102000007514 Peroxiredoxin VI Human genes 0.000 description 1
- 108010085824 Peroxiredoxin VI Proteins 0.000 description 1
- 239000005922 Phosphane Substances 0.000 description 1
- 229940123263 Phosphodiesterase 3 inhibitor Drugs 0.000 description 1
- 229940123333 Phosphodiesterase 5 inhibitor Drugs 0.000 description 1
- VQDBNKDJNJQRDG-UHFFFAOYSA-N Pirbuterol Chemical compound CC(C)(C)NCC(O)C1=CC=C(O)C(CO)=N1 VQDBNKDJNJQRDG-UHFFFAOYSA-N 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- 208000007400 Relapsing-Remitting Multiple Sclerosis Diseases 0.000 description 1
- 208000001647 Renal Insufficiency Diseases 0.000 description 1
- 108010034634 Repressor Proteins Proteins 0.000 description 1
- 102000009661 Repressor Proteins Human genes 0.000 description 1
- 208000025747 Rheumatic disease Diseases 0.000 description 1
- VPMWDFRZSIMDKW-YJYMSZOUSA-N Salmefamol Chemical compound C1=CC(OC)=CC=C1C[C@@H](C)NC[C@H](O)C1=CC=C(O)C(CO)=C1 VPMWDFRZSIMDKW-YJYMSZOUSA-N 0.000 description 1
- 101100485158 Salmonella typhimurium (strain LT2 / SGSC1412 / ATCC 700720) wzzE gene Proteins 0.000 description 1
- 206010039710 Scleroderma Diseases 0.000 description 1
- 208000034189 Sclerosis Diseases 0.000 description 1
- GIIZNNXWQWCKIB-UHFFFAOYSA-N Serevent Chemical compound C1=C(O)C(CO)=CC(C(O)CNCCCCCCOCCCCC=2C=CC=CC=2)=C1 GIIZNNXWQWCKIB-UHFFFAOYSA-N 0.000 description 1
- 229940123518 Sodium/glucose cotransporter 2 inhibitor Drugs 0.000 description 1
- YPWFISCTZQNZAU-UHFFFAOYSA-N Thiane Chemical compound C1CCSCC1 YPWFISCTZQNZAU-UHFFFAOYSA-N 0.000 description 1
- DQHNAVOVODVIMG-UHFFFAOYSA-M Tiotropium bromide Chemical compound [Br-].C1C(C2C3O2)[N+](C)(C)C3CC1OC(=O)C(O)(C=1SC=CC=1)C1=CC=CS1 DQHNAVOVODVIMG-UHFFFAOYSA-M 0.000 description 1
- 102000003978 Tissue Plasminogen Activator Human genes 0.000 description 1
- 108090000373 Tissue Plasminogen Activator Proteins 0.000 description 1
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
- 102000001400 Tryptase Human genes 0.000 description 1
- 108060005989 Tryptase Proteins 0.000 description 1
- 102000006275 Ubiquitin-Protein Ligases Human genes 0.000 description 1
- 108010083111 Ubiquitin-Protein Ligases Proteins 0.000 description 1
- 206010047163 Vasospasm Diseases 0.000 description 1
- OEXHQOGQTVQTAT-SSZRJXQFSA-N [(1r,5s)-8-methyl-8-propan-2-yl-8-azoniabicyclo[3.2.1]octan-3-yl] (2r)-3-hydroxy-2-phenylpropanoate Chemical compound C1([C@H](CO)C(=O)OC2C[C@H]3CC[C@@H](C2)[N+]3(C)C(C)C)=CC=CC=C1 OEXHQOGQTVQTAT-SSZRJXQFSA-N 0.000 description 1
- VGXACJMXDYPFDB-SXMMONRFSA-N [(3r)-1-azabicyclo[2.2.2]octan-3-yl] (2s)-2-(hydroxymethyl)-4-[(r)-methylsulfinyl]-2-phenylbutanoate Chemical compound C1([C@@](CO)(C(=O)O[C@@H]2C3CCN(CC3)C2)CC[S@](=O)C)=CC=CC=C1 VGXACJMXDYPFDB-SXMMONRFSA-N 0.000 description 1
- ANGKOCUUWGHLCE-HKUYNNGSSA-N [(3s)-1,1-dimethylpyrrolidin-1-ium-3-yl] (2r)-2-cyclopentyl-2-hydroxy-2-phenylacetate Chemical compound C1[N+](C)(C)CC[C@@H]1OC(=O)[C@](O)(C=1C=CC=CC=1)C1CCCC1 ANGKOCUUWGHLCE-HKUYNNGSSA-N 0.000 description 1
- CDKNUFNIFGPFSF-AYVLZSQQSA-N [(8s,9s,10r,11s,13s,14s,17r)-11-hydroxy-10,13-dimethyl-3-oxo-17-(2-propanoylsulfanylacetyl)-2,6,7,8,9,11,12,14,15,16-decahydro-1h-cyclopenta[a]phenanthren-17-yl] butanoate Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(=O)CSC(=O)CC)(OC(=O)CCC)[C@@]1(C)C[C@@H]2O CDKNUFNIFGPFSF-AYVLZSQQSA-N 0.000 description 1
- SJKSGJWKGXHILH-UHFFFAOYSA-N [4-(difluoromethyl)pyrimidin-5-yl]methanol Chemical compound OCc1cncnc1C(F)F SJKSGJWKGXHILH-UHFFFAOYSA-N 0.000 description 1
- WWEGUTDGLDGCSZ-UHFFFAOYSA-N [4-(trifluoromethyl)pyrimidin-5-yl]methanol Chemical compound FC(C1=NC=NC=C1CO)(F)F WWEGUTDGLDGCSZ-UHFFFAOYSA-N 0.000 description 1
- 230000001594 aberrant effect Effects 0.000 description 1
- 229960002632 acarbose Drugs 0.000 description 1
- XUFXOAAUWZOOIT-UHFFFAOYSA-N acarviostatin I01 Natural products OC1C(O)C(NC2C(C(O)C(O)C(CO)=C2)O)C(C)OC1OC(C(C1O)O)C(CO)OC1OC1C(CO)OC(O)C(O)C1O XUFXOAAUWZOOIT-UHFFFAOYSA-N 0.000 description 1
- TVWAEQRFKRTYIG-JIDHJSLPSA-N acetic acid;4-[(1r)-2-[6-[2-[(2,6-dichlorophenyl)methoxy]ethoxy]hexylamino]-1-hydroxyethyl]-2-(hydroxymethyl)phenol Chemical compound CC(O)=O.C1=C(O)C(CO)=CC([C@@H](O)CNCCCCCCOCCOCC=2C(=CC=CC=2Cl)Cl)=C1 TVWAEQRFKRTYIG-JIDHJSLPSA-N 0.000 description 1
- 229940121373 acetyl-coa carboxylase inhibitor Drugs 0.000 description 1
- 229940019903 aclidinium Drugs 0.000 description 1
- 229960005012 aclidinium bromide Drugs 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 206010051895 acute chest syndrome Diseases 0.000 description 1
- 125000005042 acyloxymethyl group Chemical group 0.000 description 1
- 108091005764 adaptor proteins Proteins 0.000 description 1
- 102000035181 adaptor proteins Human genes 0.000 description 1
- 229940077379 adcirca Drugs 0.000 description 1
- 125000005426 adeninyl group Chemical group N1=C(N=C2N=CNC2=C1N)* 0.000 description 1
- 229960005305 adenosine Drugs 0.000 description 1
- 239000000048 adrenergic agonist Substances 0.000 description 1
- 229940126157 adrenergic receptor agonist Drugs 0.000 description 1
- 238000012382 advanced drug delivery Methods 0.000 description 1
- NDAUXUAQIAJITI-UHFFFAOYSA-N albuterol Chemical compound CC(C)(C)NCC(O)C1=CC=C(O)C(CO)=C1 NDAUXUAQIAJITI-UHFFFAOYSA-N 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 125000004849 alkoxymethyl group Chemical group 0.000 description 1
- 125000005210 alkyl ammonium group Chemical group 0.000 description 1
- 125000005907 alkyl ester group Chemical group 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 239000003888 alpha glucosidase inhibitor Substances 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 229960002414 ambrisentan Drugs 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 235000019257 ammonium acetate Nutrition 0.000 description 1
- 229940043376 ammonium acetate Drugs 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 230000003178 anti-diabetic effect Effects 0.000 description 1
- 230000001028 anti-proliverative effect Effects 0.000 description 1
- 239000003472 antidiabetic agent Substances 0.000 description 1
- 230000002917 arthritic effect Effects 0.000 description 1
- 229940098165 atrovent Drugs 0.000 description 1
- 230000002238 attenuated effect Effects 0.000 description 1
- AAMATCKFMHVIDO-UHFFFAOYSA-N azane;1h-pyrrole Chemical compound N.C=1C=CNC=1 AAMATCKFMHVIDO-UHFFFAOYSA-N 0.000 description 1
- CBHOOMGKXCMKIR-UHFFFAOYSA-N azane;methanol Chemical compound N.OC CBHOOMGKXCMKIR-UHFFFAOYSA-N 0.000 description 1
- 150000001540 azides Chemical class 0.000 description 1
- ANZXOIAKUNOVQU-UHFFFAOYSA-N bambuterol Chemical compound CN(C)C(=O)OC1=CC(OC(=O)N(C)C)=CC(C(O)CNC(C)(C)C)=C1 ANZXOIAKUNOVQU-UHFFFAOYSA-N 0.000 description 1
- 229960003060 bambuterol Drugs 0.000 description 1
- 229950002483 bardoxolone Drugs 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 210000001841 basilar artery Anatomy 0.000 description 1
- NBMKJKDGKREAPL-DVTGEIKXSA-N beclomethasone Chemical class C1CC2=CC(=O)C=C[C@]2(C)[C@]2(Cl)[C@@H]1[C@@H]1C[C@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O NBMKJKDGKREAPL-DVTGEIKXSA-N 0.000 description 1
- 125000004604 benzisothiazolyl group Chemical group S1N=C(C2=C1C=CC=C2)* 0.000 description 1
- 125000004602 benzodiazinyl group Chemical group N1=NC(=CC2=C1C=CC=C2)* 0.000 description 1
- 125000002047 benzodioxolyl group Chemical group O1OC(C2=C1C=CC=C2)* 0.000 description 1
- 125000004601 benzofurazanyl group Chemical group N1=C2C(=NO1)C(=CC=C2)* 0.000 description 1
- 125000004622 benzoxazinyl group Chemical group O1NC(=CC2=C1C=CC=C2)* 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- 108010014499 beta-2 Adrenergic Receptors Proteins 0.000 description 1
- MKCBRYIXFFGIKN-UHFFFAOYSA-N bicyclo[1.1.1]pentane Chemical compound C1C2CC1C2 MKCBRYIXFFGIKN-UHFFFAOYSA-N 0.000 description 1
- JSMRMEYFZHIPJV-UHFFFAOYSA-N bicyclo[2.1.1]hexane Chemical compound C1C2CC1CC2 JSMRMEYFZHIPJV-UHFFFAOYSA-N 0.000 description 1
- GPRLTFBKWDERLU-UHFFFAOYSA-N bicyclo[2.2.2]octane Chemical group C1CC2CCC1CC2 GPRLTFBKWDERLU-UHFFFAOYSA-N 0.000 description 1
- 150000004283 biguanides Chemical class 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000008275 binding mechanism Effects 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 229960002685 biotin Drugs 0.000 description 1
- 235000020958 biotin Nutrition 0.000 description 1
- 239000011616 biotin Substances 0.000 description 1
- 239000004305 biphenyl Substances 0.000 description 1
- 235000010290 biphenyl Nutrition 0.000 description 1
- IPWKHHSGDUIRAH-UHFFFAOYSA-N bis(pinacolato)diboron Chemical compound O1C(C)(C)C(C)(C)OB1B1OC(C)(C)C(C)(C)O1 IPWKHHSGDUIRAH-UHFFFAOYSA-N 0.000 description 1
- 229910000085 borane Inorganic materials 0.000 description 1
- 229960003065 bosentan Drugs 0.000 description 1
- CODNYICXDISAEA-UHFFFAOYSA-N bromine monochloride Chemical group BrCl CODNYICXDISAEA-UHFFFAOYSA-N 0.000 description 1
- 229960004436 budesonide Drugs 0.000 description 1
- 239000006172 buffering agent Substances 0.000 description 1
- 125000004744 butyloxycarbonyl group Chemical group 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 229960001713 canagliflozin Drugs 0.000 description 1
- VHOFTEAWFCUTOS-TUGBYPPCSA-N canagliflozin hydrate Chemical compound O.CC1=CC=C([C@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)O)C=C1CC(S1)=CC=C1C1=CC=C(F)C=C1.CC1=CC=C([C@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)O)C=C1CC(S1)=CC=C1C1=CC=C(F)C=C1 VHOFTEAWFCUTOS-TUGBYPPCSA-N 0.000 description 1
- 239000007894 caplet Substances 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 125000000609 carbazolyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3NC12)* 0.000 description 1
- 125000001589 carboacyl group Chemical group 0.000 description 1
- SKOLWUPSYHWYAM-UHFFFAOYSA-N carbonodithioic O,S-acid Chemical compound SC(S)=O SKOLWUPSYHWYAM-UHFFFAOYSA-N 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 125000006244 carboxylic acid protecting group Chemical group 0.000 description 1
- 231100000357 carcinogen Toxicity 0.000 description 1
- 239000003183 carcinogenic agent Substances 0.000 description 1
- 210000000748 cardiovascular system Anatomy 0.000 description 1
- 229950010713 carmoterol Drugs 0.000 description 1
- 210000000845 cartilage Anatomy 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000002032 cellular defenses Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 206010008118 cerebral infarction Diseases 0.000 description 1
- 208000026106 cerebrovascular disease Diseases 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- FFPXPXOAFQCNBS-MRVPVSSYSA-N chembl1513993 Chemical compound N1=CC=2C(=O)NC(C[C@@H](C)C(F)(F)F)=NC=2N1C1=CC=CC=C1Cl FFPXPXOAFQCNBS-MRVPVSSYSA-N 0.000 description 1
- KEWHKYJURDBRMN-XSAPEOHZSA-M chembl2134724 Chemical compound O.[Br-].O([C@H]1C[C@H]2CC[C@@H](C1)[N+]2(C)C(C)C)C(=O)C(CO)C1=CC=CC=C1 KEWHKYJURDBRMN-XSAPEOHZSA-M 0.000 description 1
- IWXUVYOOUMLUTQ-CZUORRHYSA-N chembl2179105 Chemical compound C([C@H]([C@@H](C1)C=2NC(=O)C=3C=NN(C=3N=2)C2CCOCC2)C)N1CC1=NC=CC=N1 IWXUVYOOUMLUTQ-CZUORRHYSA-N 0.000 description 1
- 239000002559 chemokine receptor antagonist Substances 0.000 description 1
- 238000004296 chiral HPLC Methods 0.000 description 1
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
- 229960001231 choline Drugs 0.000 description 1
- 239000000812 cholinergic antagonist Substances 0.000 description 1
- 210000003483 chromatin Anatomy 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 125000004230 chromenyl group Chemical group O1C(C=CC2=CC=CC=C12)* 0.000 description 1
- 208000037976 chronic inflammation Diseases 0.000 description 1
- 230000006020 chronic inflammation Effects 0.000 description 1
- 229960003728 ciclesonide Drugs 0.000 description 1
- 235000019504 cigarettes Nutrition 0.000 description 1
- LOUPRKONTZGTKE-UHFFFAOYSA-N cinchonine Natural products C1C(C(C2)C=C)CCN2C1C(O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-UHFFFAOYSA-N 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 229960001117 clenbuterol Drugs 0.000 description 1
- STJMRWALKKWQGH-UHFFFAOYSA-N clenbuterol Chemical compound CC(C)(C)NCC(O)C1=CC(Cl)=C(N)C(Cl)=C1 STJMRWALKKWQGH-UHFFFAOYSA-N 0.000 description 1
- 238000011278 co-treatment Methods 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 238000011284 combination treatment Methods 0.000 description 1
- 235000008504 concentrate Nutrition 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 230000006552 constitutive activation Effects 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 239000003246 corticosteroid Substances 0.000 description 1
- 239000006184 cosolvent Substances 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 239000010779 crude oil Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 101150113466 cul-3 gene Proteins 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 230000016396 cytokine production Effects 0.000 description 1
- 230000001086 cytosolic effect Effects 0.000 description 1
- 229960003834 dapagliflozin Drugs 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- 238000012217 deletion Methods 0.000 description 1
- 230000037430 deletion Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000010511 deprotection reaction Methods 0.000 description 1
- 238000001784 detoxification Methods 0.000 description 1
- 229960003957 dexamethasone Drugs 0.000 description 1
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 1
- 229920003045 dextran sodium sulfate Polymers 0.000 description 1
- CBWJKNQKWLEEPG-UHFFFAOYSA-N dihydridoborate(1-) Chemical compound [BH2-] CBWJKNQKWLEEPG-UHFFFAOYSA-N 0.000 description 1
- 239000000539 dimer Substances 0.000 description 1
- IUNMPGNGSSIWFP-UHFFFAOYSA-N dimethylaminopropylamine Chemical compound CN(C)CCCN IUNMPGNGSSIWFP-UHFFFAOYSA-N 0.000 description 1
- 125000000532 dioxanyl group Chemical group 0.000 description 1
- 239000003603 dipeptidyl peptidase IV inhibitor Substances 0.000 description 1
- FVTWTVQXNAJTQP-UHFFFAOYSA-N diphenyl-[1-(2-phenylmethoxyethyl)-1-azoniabicyclo[2.2.2]octan-4-yl]methanol Chemical compound C=1C=CC=CC=1C(C12CC[N+](CCOCC=3C=CC=CC=3)(CC1)CC2)(O)C1=CC=CC=C1 FVTWTVQXNAJTQP-UHFFFAOYSA-N 0.000 description 1
- 208000016097 disease of metabolism Diseases 0.000 description 1
- 230000005750 disease progression Effects 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 238000009509 drug development Methods 0.000 description 1
- 229960005175 dulaglutide Drugs 0.000 description 1
- 108010005794 dulaglutide Proteins 0.000 description 1
- 239000012636 effector Substances 0.000 description 1
- 229950001279 elafibranor Drugs 0.000 description 1
- 239000003602 elastase inhibitor Substances 0.000 description 1
- 239000012039 electrophile Substances 0.000 description 1
- 238000000132 electrospray ionisation Methods 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 229960003345 empagliflozin Drugs 0.000 description 1
- OBWASQILIWPZMG-QZMOQZSNSA-N empagliflozin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1C1=CC=C(Cl)C(CC=2C=CC(O[C@@H]3COCC3)=CC=2)=C1 OBWASQILIWPZMG-QZMOQZSNSA-N 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 150000002081 enamines Chemical class 0.000 description 1
- 239000007920 enema Substances 0.000 description 1
- 229940095399 enema Drugs 0.000 description 1
- 229960001123 epoprostenol Drugs 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- 210000000267 erythroid cell Anatomy 0.000 description 1
- 229950002751 etanterol Drugs 0.000 description 1
- FTKASJMIPSSXBP-UHFFFAOYSA-N ethyl 2-nitroacetate Chemical compound CCOC(=O)C[N+]([O-])=O FTKASJMIPSSXBP-UHFFFAOYSA-N 0.000 description 1
- ASVSADXMAJRJGA-UHFFFAOYSA-N ethyl 5,5-dimethyl-4H-1,2-oxazole-3-carboxylate Chemical compound C(C)OC(=O)C1=NOC(C1)(C)C ASVSADXMAJRJGA-UHFFFAOYSA-N 0.000 description 1
- IMODJADNJWCUFZ-UHFFFAOYSA-N ethyl 5-(difluoromethyl)-1-methyltriazole-4-carboxylate Chemical compound CCOC(=O)c1nnn(C)c1C(F)F IMODJADNJWCUFZ-UHFFFAOYSA-N 0.000 description 1
- PQVSTLUFSYVLTO-UHFFFAOYSA-N ethyl n-ethoxycarbonylcarbamate Chemical compound CCOC(=O)NC(=O)OCC PQVSTLUFSYVLTO-UHFFFAOYSA-N 0.000 description 1
- 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 229960001519 exenatide Drugs 0.000 description 1
- 239000003889 eye drop Substances 0.000 description 1
- 229940012356 eye drops Drugs 0.000 description 1
- 229940121360 farnesoid X receptor (fxr) agonists Drugs 0.000 description 1
- 229960001022 fenoterol Drugs 0.000 description 1
- 230000004761 fibrosis Effects 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 229940001440 flolan Drugs 0.000 description 1
- 229960000676 flunisolide Drugs 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 125000003709 fluoroalkyl group Chemical group 0.000 description 1
- 229960001469 fluticasone furoate Drugs 0.000 description 1
- XTULMSXFIHGYFS-VLSRWLAYSA-N fluticasone furoate Chemical compound O([C@]1([C@@]2(C)C[C@H](O)[C@]3(F)[C@@]4(C)C=CC(=O)C=C4[C@@H](F)C[C@H]3[C@@H]2C[C@H]1C)C(=O)SCF)C(=O)C1=CC=CO1 XTULMSXFIHGYFS-VLSRWLAYSA-N 0.000 description 1
- 229960000289 fluticasone propionate Drugs 0.000 description 1
- WMWTYOKRWGGJOA-CENSZEJFSA-N fluticasone propionate Chemical compound C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@]1(F)[C@@H]2[C@@H]2C[C@@H](C)[C@@](C(=O)SCF)(OC(=O)CC)[C@@]2(C)C[C@@H]1O WMWTYOKRWGGJOA-CENSZEJFSA-N 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 229960002848 formoterol Drugs 0.000 description 1
- BPZSYCZIITTYBL-UHFFFAOYSA-N formoterol Chemical compound C1=CC(OC)=CC=C1CC(C)NCC(O)C1=CC=C(O)C(NC=O)=C1 BPZSYCZIITTYBL-UHFFFAOYSA-N 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 125000003838 furazanyl group Chemical group 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 230000009395 genetic defect Effects 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- AFLFKFHDSCQHOL-IZZDOVSWSA-N gft505 Chemical compound C1=CC(SC)=CC=C1C(=O)\C=C\C1=CC(C)=C(OC(C)(C)C(O)=O)C(C)=C1 AFLFKFHDSCQHOL-IZZDOVSWSA-N 0.000 description 1
- WIGIZIANZCJQQY-RUCARUNLSA-N glimepiride Chemical compound O=C1C(CC)=C(C)CN1C(=O)NCCC1=CC=C(S(=O)(=O)NC(=O)N[C@@H]2CC[C@@H](C)CC2)C=C1 WIGIZIANZCJQQY-RUCARUNLSA-N 0.000 description 1
- 229960004346 glimepiride Drugs 0.000 description 1
- 210000000585 glomerular basement membrane Anatomy 0.000 description 1
- 230000024924 glomerular filtration Effects 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 230000009229 glucose formation Effects 0.000 description 1
- 229960002462 glycopyrronium bromide Drugs 0.000 description 1
- 239000003979 granulating agent Substances 0.000 description 1
- 230000002140 halogenating effect Effects 0.000 description 1
- 238000003306 harvesting Methods 0.000 description 1
- 208000038002 heart failure with reduced ejection fraction Diseases 0.000 description 1
- 230000004217 heart function Effects 0.000 description 1
- BTIJJDXEELBZFS-QDUVMHSLSA-K hemin Chemical compound CC1=C(CCC(O)=O)C(C=C2C(CCC(O)=O)=C(C)\C(N2[Fe](Cl)N23)=C\4)=N\C1=C/C2=C(C)C(C=C)=C3\C=C/1C(C)=C(C=C)C/4=N\1 BTIJJDXEELBZFS-QDUVMHSLSA-K 0.000 description 1
- 229940025294 hemin Drugs 0.000 description 1
- 208000034737 hemoglobinopathy Diseases 0.000 description 1
- 230000008588 hemolysis Effects 0.000 description 1
- 208000007475 hemolytic anemia Diseases 0.000 description 1
- 230000002440 hepatic effect Effects 0.000 description 1
- GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 1
- 230000003284 homeostatic effect Effects 0.000 description 1
- 230000013632 homeostatic process Effects 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- 150000002430 hydrocarbons Chemical group 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 229960001330 hydroxycarbamide Drugs 0.000 description 1
- SKOWZLGOFVSKLB-UHFFFAOYSA-N hypodiboric acid Chemical compound OB(O)B(O)O SKOWZLGOFVSKLB-UHFFFAOYSA-N 0.000 description 1
- 229960002240 iloprost Drugs 0.000 description 1
- 150000002466 imines Chemical class 0.000 description 1
- 210000002865 immune cell Anatomy 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 230000001976 improved effect Effects 0.000 description 1
- MGXWVYUBJRZYPE-YUGYIWNOSA-N incretin Chemical class C([C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC(N)=O)C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1C=CC(O)=CC=1)[C@@H](C)O)[C@@H](C)CC)C1=CC=C(O)C=C1 MGXWVYUBJRZYPE-YUGYIWNOSA-N 0.000 description 1
- 239000000859 incretin Substances 0.000 description 1
- QZZUEBNBZAPZLX-QFIPXVFZSA-N indacaterol Chemical compound N1C(=O)C=CC2=C1C(O)=CC=C2[C@@H](O)CNC1CC(C=C(C(=C2)CC)CC)=C2C1 QZZUEBNBZAPZLX-QFIPXVFZSA-N 0.000 description 1
- 229960004078 indacaterol Drugs 0.000 description 1
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
- 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 230000004968 inflammatory condition Effects 0.000 description 1
- 208000027866 inflammatory disease Diseases 0.000 description 1
- 230000028709 inflammatory response Effects 0.000 description 1
- 230000008798 inflammatory stress Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 208000018337 inherited hemoglobinopathy Diseases 0.000 description 1
- 208000030309 inherited neurodegenerative disease Diseases 0.000 description 1
- 150000002485 inorganic esters Chemical class 0.000 description 1
- 239000004026 insulin derivative Substances 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 238000001361 intraarterial administration Methods 0.000 description 1
- 238000007913 intrathecal administration Methods 0.000 description 1
- 229910052740 iodine Chemical group 0.000 description 1
- 239000011630 iodine Chemical group 0.000 description 1
- OEXHQOGQTVQTAT-JRNQLAHRSA-N ipratropium Chemical compound O([C@H]1C[C@H]2CC[C@@H](C1)[N@@+]2(C)C(C)C)C(=O)C(CO)C1=CC=CC=C1 OEXHQOGQTVQTAT-JRNQLAHRSA-N 0.000 description 1
- 229960001888 ipratropium Drugs 0.000 description 1
- 208000028867 ischemia Diseases 0.000 description 1
- OWFXIOWLTKNBAP-UHFFFAOYSA-N isoamyl nitrite Chemical compound CC(C)CCON=O OWFXIOWLTKNBAP-UHFFFAOYSA-N 0.000 description 1
- 125000001977 isobenzofuranyl group Chemical group C=1(OC=C2C=CC=CC12)* 0.000 description 1
- 125000003384 isochromanyl group Chemical group C1(OCCC2=CC=CC=C12)* 0.000 description 1
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
- 125000005956 isoquinolyl group Chemical group 0.000 description 1
- 210000002510 keratinocyte Anatomy 0.000 description 1
- 230000002361 ketogenic effect Effects 0.000 description 1
- 125000000468 ketone group Chemical group 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 201000006370 kidney failure Diseases 0.000 description 1
- 230000003907 kidney function Effects 0.000 description 1
- 150000002596 lactones Chemical class 0.000 description 1
- 201000010901 lateral sclerosis Diseases 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 229940090243 letairis Drugs 0.000 description 1
- 231100000225 lethality Toxicity 0.000 description 1
- 239000003199 leukotriene receptor blocking agent Substances 0.000 description 1
- 150000002617 leukotrienes Chemical class 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 229960002701 liraglutide Drugs 0.000 description 1
- GLXDVVHUTZTUQK-UHFFFAOYSA-M lithium hydroxide monohydrate Substances [Li+].O.[OH-] GLXDVVHUTZTUQK-UHFFFAOYSA-M 0.000 description 1
- 229940040692 lithium hydroxide monohydrate Drugs 0.000 description 1
- 229910001947 lithium oxide Inorganic materials 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 210000005265 lung cell Anatomy 0.000 description 1
- 206010025135 lupus erythematosus Diseases 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 238000011418 maintenance treatment Methods 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 238000002483 medication Methods 0.000 description 1
- 229950004994 meglitinide Drugs 0.000 description 1
- 101150089110 metN gene Proteins 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- XZWYZXLIPXDOLR-UHFFFAOYSA-N metformin Chemical compound CN(C)C(=N)NC(N)=N XZWYZXLIPXDOLR-UHFFFAOYSA-N 0.000 description 1
- 229960003105 metformin Drugs 0.000 description 1
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 1
- SZUYCZFYLJAJTF-UHFFFAOYSA-N methyl 4,5,6,7-tetrahydrotriazolo[1,5-a]pyridine-3-carboxylate Chemical compound N1=NC(=C2N1CCCC2)C(=O)OC SZUYCZFYLJAJTF-UHFFFAOYSA-N 0.000 description 1
- YSVBTANYFUGPMM-UHFFFAOYSA-N methyl 4-ethenyl-5-methyl-1,2-oxazole-3-carboxylate Chemical compound CC1=C(C(=NO1)C(=O)OC)C=C YSVBTANYFUGPMM-UHFFFAOYSA-N 0.000 description 1
- FHFNGADSTGYWBH-UHFFFAOYSA-N methyl 4-formyl-5-methyl-1,2-oxazole-3-carboxylate Chemical compound C(=O)C=1C(=NOC=1C)C(=O)OC FHFNGADSTGYWBH-UHFFFAOYSA-N 0.000 description 1
- DEYIKAFKPHDCCP-UHFFFAOYSA-N methyl 4-iodo-5-methyl-1,2-oxazole-3-carboxylate Chemical compound COC(=O)C1=NOC(C)=C1I DEYIKAFKPHDCCP-UHFFFAOYSA-N 0.000 description 1
- KORGSPVXZITZFH-UHFFFAOYSA-N methyl 5-methyl-4-(trifluoromethyl)-1,2-oxazole-3-carboxylate Chemical compound COC(=O)c1noc(C)c1C(F)(F)F KORGSPVXZITZFH-UHFFFAOYSA-N 0.000 description 1
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 1
- 230000003278 mimic effect Effects 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 230000004065 mitochondrial dysfunction Effects 0.000 description 1
- 230000004898 mitochondrial function Effects 0.000 description 1
- QLIIKPVHVRXHRI-CXSFZGCWSA-N mometasone Chemical class C1CC2=CC(=O)C=C[C@]2(C)[C@]2(Cl)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CCl)(O)[C@@]1(C)C[C@@H]2O QLIIKPVHVRXHRI-CXSFZGCWSA-N 0.000 description 1
- 229960002744 mometasone furoate Drugs 0.000 description 1
- WOFMFGQZHJDGCX-ZULDAHANSA-N mometasone furoate Chemical compound O([C@]1([C@@]2(C)C[C@H](O)[C@]3(Cl)[C@@]4(C)C=CC(=O)C=C4CC[C@H]3[C@@H]2C[C@H]1C)C(=O)CCl)C(=O)C1=CC=CO1 WOFMFGQZHJDGCX-ZULDAHANSA-N 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 229960005127 montelukast Drugs 0.000 description 1
- 125000002757 morpholinyl group Chemical group 0.000 description 1
- 208000005264 motor neuron disease Diseases 0.000 description 1
- 230000002107 myocardial effect Effects 0.000 description 1
- 210000004165 myocardium Anatomy 0.000 description 1
- 229950000514 naminterol Drugs 0.000 description 1
- 239000007922 nasal spray Substances 0.000 description 1
- 229940097496 nasal spray Drugs 0.000 description 1
- 229960002259 nedocromil sodium Drugs 0.000 description 1
- 230000003959 neuroinflammation Effects 0.000 description 1
- 210000000440 neutrophil Anatomy 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 125000000018 nitroso group Chemical group N(=O)* 0.000 description 1
- FBUKVWPVBMHYJY-UHFFFAOYSA-N nonanoic acid Chemical compound CCCCCCCCC(O)=O FBUKVWPVBMHYJY-UHFFFAOYSA-N 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 238000010899 nucleation Methods 0.000 description 1
- 239000012038 nucleophile Substances 0.000 description 1
- 210000004940 nucleus Anatomy 0.000 description 1
- ZXERDUOLZKYMJM-ZWECCWDJSA-N obeticholic acid Chemical compound C([C@@]12C)C[C@@H](O)C[C@H]1[C@@H](CC)[C@@H](O)[C@@H]1[C@@H]2CC[C@]2(C)[C@@H]([C@H](C)CCC(O)=O)CC[C@H]21 ZXERDUOLZKYMJM-ZWECCWDJSA-N 0.000 description 1
- 229960001601 obeticholic acid Drugs 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 229960004286 olodaterol Drugs 0.000 description 1
- COUYJEVMBVSIHV-SFHVURJKSA-N olodaterol Chemical compound C1=CC(OC)=CC=C1CC(C)(C)NC[C@H](O)C1=CC(O)=CC2=C1OCC(=O)N2 COUYJEVMBVSIHV-SFHVURJKSA-N 0.000 description 1
- 229950008128 omaveloxolone Drugs 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 230000004768 organ dysfunction Effects 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 239000012285 osmium tetroxide Substances 0.000 description 1
- 229910000489 osmium tetroxide Inorganic materials 0.000 description 1
- YEWPVCUHKJABMV-UHFFFAOYSA-N oxane-3-carboxylic acid Chemical compound OC(=O)C1CCCOC1 YEWPVCUHKJABMV-UHFFFAOYSA-N 0.000 description 1
- 125000003566 oxetanyl group Chemical group 0.000 description 1
- 230000004792 oxidative damage Effects 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 150000002923 oximes Chemical class 0.000 description 1
- 125000000466 oxiranyl group Chemical group 0.000 description 1
- NVOYVOBDTVTBDX-PMEUIYRNSA-N oxitropium Chemical compound CC[N+]1(C)[C@H]2C[C@@H](C[C@@H]1[C@H]1O[C@@H]21)OC(=O)[C@H](CO)C1=CC=CC=C1 NVOYVOBDTVTBDX-PMEUIYRNSA-N 0.000 description 1
- 229960000797 oxitropium Drugs 0.000 description 1
- 125000005476 oxopyrrolidinyl group Chemical group 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 230000009054 pathological process Effects 0.000 description 1
- 230000008289 pathophysiological mechanism Effects 0.000 description 1
- 230000007310 pathophysiology Effects 0.000 description 1
- 125000005010 perfluoroalkyl group Chemical group 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 210000004786 perivascular cell Anatomy 0.000 description 1
- 150000004965 peroxy acids Chemical class 0.000 description 1
- 229940124531 pharmaceutical excipient Drugs 0.000 description 1
- 230000006611 pharmacological activation Effects 0.000 description 1
- 238000009522 phase III clinical trial Methods 0.000 description 1
- 125000001791 phenazinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3N=C12)* 0.000 description 1
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
- 229910000064 phosphane Inorganic materials 0.000 description 1
- 239000002570 phosphodiesterase III inhibitor Substances 0.000 description 1
- 239000002590 phosphodiesterase V inhibitor Substances 0.000 description 1
- 229940043441 phosphoinositide 3-kinase inhibitor Drugs 0.000 description 1
- 150000003014 phosphoric acid esters Chemical class 0.000 description 1
- 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 1
- 125000000612 phthaloyl group Chemical group C(C=1C(C(=O)*)=CC=CC1)(=O)* 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 229960005095 pioglitazone Drugs 0.000 description 1
- 229960005414 pirbuterol Drugs 0.000 description 1
- 239000000902 placebo Substances 0.000 description 1
- 229940068196 placebo Drugs 0.000 description 1
- 239000004014 plasticizer Substances 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 238000010837 poor prognosis Methods 0.000 description 1
- 230000008092 positive effect Effects 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- OIGNJSKKLXVSLS-VWUMJDOOSA-N prednisolone Chemical compound O=C1C=C[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 OIGNJSKKLXVSLS-VWUMJDOOSA-N 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 230000000770 proinflammatory effect Effects 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 description 1
- 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
- 229940127293 prostanoid Drugs 0.000 description 1
- 150000003814 prostanoids Chemical class 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 230000004063 proteosomal degradation Effects 0.000 description 1
- 230000007111 proteostasis Effects 0.000 description 1
- 239000003379 purinergic P1 receptor agonist Substances 0.000 description 1
- 239000000296 purinergic P1 receptor antagonist Substances 0.000 description 1
- VIXWGKYSYIBATJ-UHFFFAOYSA-N pyrrol-2-one Chemical compound O=C1C=CC=N1 VIXWGKYSYIBATJ-UHFFFAOYSA-N 0.000 description 1
- MIXMJCQRHVAJIO-TZHJZOAOSA-N qk4dys664x Chemical compound O.C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@@H]1[C@@H]2[C@@H]2C[C@H]3OC(C)(C)O[C@@]3(C(=O)CO)[C@@]2(C)C[C@@H]1O.C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@@H]1[C@@H]2[C@@H]2C[C@H]3OC(C)(C)O[C@@]3(C(=O)CO)[C@@]2(C)C[C@@H]1O MIXMJCQRHVAJIO-TZHJZOAOSA-N 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 229960001404 quinidine Drugs 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 125000005493 quinolyl group Chemical group 0.000 description 1
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000010282 redox signaling Effects 0.000 description 1
- 229960003614 regadenoson Drugs 0.000 description 1
- 229940118867 remodulin Drugs 0.000 description 1
- 229960002354 repaglinide Drugs 0.000 description 1
- WVLAAKXASPCBGT-UHFFFAOYSA-N reproterol Chemical compound C1=2C(=O)N(C)C(=O)N(C)C=2N=CN1CCCNCC(O)C1=CC(O)=CC(O)=C1 WVLAAKXASPCBGT-UHFFFAOYSA-N 0.000 description 1
- 229960002720 reproterol Drugs 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 208000023504 respiratory system disease Diseases 0.000 description 1
- 210000001525 retina Anatomy 0.000 description 1
- 229940039245 revatio Drugs 0.000 description 1
- 229950000915 revatropate Drugs 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 238000007142 ring opening reaction Methods 0.000 description 1
- 125000006413 ring segment Chemical group 0.000 description 1
- 229950002845 rivipansel Drugs 0.000 description 1
- 238000011808 rodent model Methods 0.000 description 1
- 229950004432 rofleponide Drugs 0.000 description 1
- IXTCZMJQGGONPY-XJAYAHQCSA-N rofleponide Chemical compound C1([C@@H](F)C2)=CC(=O)CC[C@]1(C)[C@]1(F)[C@@H]2[C@@H]2C[C@H]3O[C@@H](CCC)O[C@@]3(C(=O)CO)[C@@]2(C)C[C@@H]1O IXTCZMJQGGONPY-XJAYAHQCSA-N 0.000 description 1
- 229960002052 salbutamol Drugs 0.000 description 1
- 229950001879 salmefamol Drugs 0.000 description 1
- 229960004017 salmeterol Drugs 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- YIDDLAAKOYYGJG-UHFFFAOYSA-N selonsertib Chemical compound CC(C)N1C=NN=C1C1=CC=CC(NC(=O)C=2C(=CC(C)=C(C=2)N2C=C(N=C2)C2CC2)F)=N1 YIDDLAAKOYYGJG-UHFFFAOYSA-N 0.000 description 1
- 229950003181 selonsertib Drugs 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 229960003310 sildenafil Drugs 0.000 description 1
- 238000009097 single-agent therapy Methods 0.000 description 1
- MFFMDFFZMYYVKS-SECBINFHSA-N sitagliptin Chemical compound C([C@H](CC(=O)N1CC=2N(C(=NN=2)C(F)(F)F)CC1)N)C1=CC(F)=C(F)C=C1F MFFMDFFZMYYVKS-SECBINFHSA-N 0.000 description 1
- 229960004034 sitagliptin Drugs 0.000 description 1
- 230000037380 skin damage Effects 0.000 description 1
- 208000017520 skin disease Diseases 0.000 description 1
- 230000000391 smoking effect Effects 0.000 description 1
- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 1
- 230000003381 solubilizing effect Effects 0.000 description 1
- 229940046810 spiriva Drugs 0.000 description 1
- DQHNAVOVODVIMG-RGECMCKFSA-M spiriva Chemical compound [Br-].C([C@@H]1[N+]([C@H](C2)[C@@H]3[C@H]1O3)(C)C)C2OC(=O)C(O)(C=1SC=CC=1)C1=CC=CS1 DQHNAVOVODVIMG-RGECMCKFSA-M 0.000 description 1
- HEMCGZPSGYRIOL-UHFFFAOYSA-N spiro[2.4]heptane Chemical compound C1CC11CCCC1 HEMCGZPSGYRIOL-UHFFFAOYSA-N 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 150000003457 sulfones Chemical group 0.000 description 1
- 150000003462 sulfoxides Chemical class 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- IEHKWSGCTWLXFU-IIBYNOLFSA-N tadalafil Chemical compound C1=C2OCOC2=CC([C@@H]2C3=C([C]4C=CC=CC4=N3)C[C@H]3N2C(=O)CN(C3=O)C)=C1 IEHKWSGCTWLXFU-IIBYNOLFSA-N 0.000 description 1
- WOXKDUGGOYFFRN-IIBYNOLFSA-N tadalafil Chemical compound C1=C2OCOC2=CC([C@@H]2C3=C(C4=CC=CC=C4N3)C[C@H]3N2C(=O)CN(C3=O)C)=C1 WOXKDUGGOYFFRN-IIBYNOLFSA-N 0.000 description 1
- 229960000835 tadalafil Drugs 0.000 description 1
- 229940121136 tecfidera Drugs 0.000 description 1
- 229960000195 terbutaline Drugs 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- 125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 1
- 125000000383 tetramethylene group Chemical group [H]C([H])([*:1])C([H])([H])C([H])([H])C([H])([H])[*:2] 0.000 description 1
- 229960000278 theophylline Drugs 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 150000001467 thiazolidinediones Chemical class 0.000 description 1
- JWCVYQRPINPYQJ-UHFFFAOYSA-N thiepane Chemical compound C1CCCSCC1 JWCVYQRPINPYQJ-UHFFFAOYSA-N 0.000 description 1
- 125000000464 thioxo group Chemical group S=* 0.000 description 1
- OEKWJQXRCDYSHL-FNOIDJSQSA-N ticagrelor Chemical compound C1([C@@H]2C[C@H]2NC=2N=C(N=C3N([C@H]4[C@@H]([C@H](O)[C@@H](OCCO)C4)O)N=NC3=2)SCCC)=CC=C(F)C(F)=C1 OEKWJQXRCDYSHL-FNOIDJSQSA-N 0.000 description 1
- 229960002528 ticagrelor Drugs 0.000 description 1
- LERNTVKEWCAPOY-DZZGSBJMSA-N tiotropium Chemical compound O([C@H]1C[C@@H]2[N+]([C@H](C1)[C@@H]1[C@H]2O1)(C)C)C(=O)C(O)(C=1SC=CC=1)C1=CC=CS1 LERNTVKEWCAPOY-DZZGSBJMSA-N 0.000 description 1
- 229940110309 tiotropium Drugs 0.000 description 1
- 229960000187 tissue plasminogen activator Drugs 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 229940118436 tracleer Drugs 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000009261 transgenic effect Effects 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- YNDXUCZADRHECN-JNQJZLCISA-N triamcinolone acetonide Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@H]3OC(C)(C)O[C@@]3(C(=O)CO)[C@@]1(C)C[C@@H]2O YNDXUCZADRHECN-JNQJZLCISA-N 0.000 description 1
- 229960002117 triamcinolone acetonide Drugs 0.000 description 1
- 125000004306 triazinyl group Chemical group 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- UORVGPXVDQYIDP-UHFFFAOYSA-N trihydridoboron Substances B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 1
- 239000002750 tryptase inhibitor Substances 0.000 description 1
- 210000005239 tubule Anatomy 0.000 description 1
- 230000002100 tumorsuppressive effect Effects 0.000 description 1
- 229940014025 tyvaso Drugs 0.000 description 1
- 229960004258 umeclidinium Drugs 0.000 description 1
- 230000000304 vasodilatating effect Effects 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 229940105295 ventavis Drugs 0.000 description 1
- 229960004026 vilanterol Drugs 0.000 description 1
- LVLANIHJQRZTPY-UHFFFAOYSA-N vinyl carbamate Chemical compound NC(=O)OC=C LVLANIHJQRZTPY-UHFFFAOYSA-N 0.000 description 1
- 239000003039 volatile agent Substances 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 230000029663 wound healing Effects 0.000 description 1
- 238000002424 x-ray crystallography Methods 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing three or more hetero rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/472—Non-condensed isoquinolines, e.g. papaverine
- A61K31/4725—Non-condensed isoquinolines, e.g. papaverine containing further heterocyclic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D498/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB1817193.4A GB201817193D0 (en) | 2018-10-22 | 2018-10-22 | Tetrahydroisoquinoline compounds |
| GBGB1907674.4A GB201907674D0 (en) | 2019-05-30 | 2019-05-30 | Tetrahydroisoquinoline compounds |
| PCT/GB2019/053012 WO2020084300A1 (en) | 2018-10-22 | 2019-10-22 | Therapeutic compounds |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2963613T3 true ES2963613T3 (es) | 2024-04-01 |
Family
ID=68393021
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES19795615T Active ES2963613T3 (es) | 2018-10-22 | 2019-10-22 | Compuestos terapéuticos |
Country Status (23)
| Country | Link |
|---|---|
| US (1) | US20220002286A1 (ja) |
| EP (2) | EP4252755A3 (ja) |
| JP (1) | JP2022514437A (ja) |
| KR (1) | KR20210080474A (ja) |
| CN (1) | CN112996785A (ja) |
| AU (1) | AU2019364717B2 (ja) |
| BR (1) | BR112021007513A2 (ja) |
| CA (1) | CA3114859A1 (ja) |
| DK (1) | DK3870578T3 (ja) |
| ES (1) | ES2963613T3 (ja) |
| FI (1) | FI3870578T3 (ja) |
| HR (1) | HRP20231306T1 (ja) |
| HU (1) | HUE064111T2 (ja) |
| IL (1) | IL282330A (ja) |
| LT (1) | LT3870578T (ja) |
| MX (1) | MX2021004566A (ja) |
| PH (1) | PH12021550872A1 (ja) |
| PL (1) | PL3870578T3 (ja) |
| PT (1) | PT3870578T (ja) |
| RS (1) | RS64836B1 (ja) |
| SG (1) | SG11202103253YA (ja) |
| SI (1) | SI3870578T1 (ja) |
| WO (1) | WO2020084300A1 (ja) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP4364804A2 (en) | 2018-08-20 | 2024-05-08 | Janssen Pharmaceutica NV | Inhibitors of keap1-nrf2 protein-protein interaction |
| GB202005863D0 (en) * | 2020-04-22 | 2020-06-03 | C4X Discovery Ltd | Therapeutic compounds |
| GB202005852D0 (en) * | 2020-04-22 | 2020-06-03 | C4X Discovery Ltd | Therapeutic compounds |
| CN114507181B (zh) * | 2020-11-17 | 2024-03-26 | 中国医学科学院药物研究所 | 含5-取代四氢异喹啉的丙酸类化合物、其药物组合物和应用 |
| WO2023073364A1 (en) | 2021-10-25 | 2023-05-04 | C4X Discovery Limited | Tetrahydroisoquinoline compounds that are keap1 binders |
| AR128216A1 (es) * | 2022-01-07 | 2024-04-10 | Chugai Pharmaceutical Co Ltd | Compuesto heterocíclico que contiene nitrógeno que tiene un efecto de activación del nrf2 |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2899183B1 (en) * | 2011-10-14 | 2018-09-19 | Bristol-Myers Squibb Company | Substituted Tetrahydroisoquinoline Compounds as Factor Xia Inhibitors |
| GB202005863D0 (en) * | 2020-04-22 | 2020-06-03 | C4X Discovery Ltd | Therapeutic compounds |
| GB202005852D0 (en) * | 2020-04-22 | 2020-06-03 | C4X Discovery Ltd | Therapeutic compounds |
-
2019
- 2019-10-22 LT LTEPPCT/GB2019/053012T patent/LT3870578T/lt unknown
- 2019-10-22 HU HUE19795615A patent/HUE064111T2/hu unknown
- 2019-10-22 CA CA3114859A patent/CA3114859A1/en active Pending
- 2019-10-22 RS RS20231069A patent/RS64836B1/sr unknown
- 2019-10-22 PT PT197956154T patent/PT3870578T/pt unknown
- 2019-10-22 BR BR112021007513-5A patent/BR112021007513A2/pt unknown
- 2019-10-22 WO PCT/GB2019/053012 patent/WO2020084300A1/en active Application Filing
- 2019-10-22 JP JP2021546488A patent/JP2022514437A/ja active Pending
- 2019-10-22 SG SG11202103253YA patent/SG11202103253YA/en unknown
- 2019-10-22 SI SI201930662T patent/SI3870578T1/sl unknown
- 2019-10-22 PL PL19795615.4T patent/PL3870578T3/pl unknown
- 2019-10-22 KR KR1020217015269A patent/KR20210080474A/ko unknown
- 2019-10-22 US US17/287,942 patent/US20220002286A1/en active Pending
- 2019-10-22 CN CN201980071533.XA patent/CN112996785A/zh active Pending
- 2019-10-22 EP EP23191389.8A patent/EP4252755A3/en active Pending
- 2019-10-22 EP EP19795615.4A patent/EP3870578B1/en active Active
- 2019-10-22 ES ES19795615T patent/ES2963613T3/es active Active
- 2019-10-22 AU AU2019364717A patent/AU2019364717B2/en active Active
- 2019-10-22 MX MX2021004566A patent/MX2021004566A/es unknown
- 2019-10-22 DK DK19795615.4T patent/DK3870578T3/da active
- 2019-10-22 FI FIEP19795615.4T patent/FI3870578T3/fi active
- 2019-10-22 HR HRP20231306TT patent/HRP20231306T1/hr unknown
-
2021
- 2021-04-14 IL IL282330A patent/IL282330A/en unknown
- 2021-04-19 PH PH12021550872A patent/PH12021550872A1/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| JP2022514437A (ja) | 2022-02-10 |
| PH12021550872A1 (en) | 2021-12-06 |
| EP4252755A3 (en) | 2023-11-08 |
| WO2020084300A1 (en) | 2020-04-30 |
| BR112021007513A2 (pt) | 2021-07-27 |
| LT3870578T (lt) | 2023-12-11 |
| PT3870578T (pt) | 2023-11-15 |
| DK3870578T3 (da) | 2023-11-13 |
| HUE064111T2 (hu) | 2024-02-28 |
| PL3870578T3 (pl) | 2024-03-04 |
| HRP20231306T1 (hr) | 2024-02-02 |
| AU2019364717A1 (en) | 2021-06-03 |
| EP3870578A1 (en) | 2021-09-01 |
| SG11202103253YA (en) | 2021-05-28 |
| CA3114859A1 (en) | 2020-04-30 |
| US20220002286A1 (en) | 2022-01-06 |
| CN112996785A (zh) | 2021-06-18 |
| AU2019364717B2 (en) | 2023-07-20 |
| SI3870578T1 (sl) | 2024-02-29 |
| IL282330A (en) | 2021-05-31 |
| EP3870578B1 (en) | 2023-08-16 |
| RS64836B1 (sr) | 2023-12-29 |
| EP4252755A2 (en) | 2023-10-04 |
| MX2021004566A (es) | 2021-06-08 |
| KR20210080474A (ko) | 2021-06-30 |
| FI3870578T3 (fi) | 2023-11-03 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ES2963613T3 (es) | Compuestos terapéuticos | |
| ES2866152T3 (es) | Derivados de tirosina amida como inhibidores de la Rho-quinasa | |
| JP5785189B2 (ja) | Ｃ型肝炎ウイルス阻害剤 | |
| TWI476190B (zh) | Ｃ型肝炎病毒抑制劑 | |
| TWI699364B (zh) | ５-氯-２-二氟甲氧基苯基吡唑并嘧啶化合物、組合物及其使用方法 | |
| JP5615352B2 (ja) | Ｃ型肝炎ウイルス阻害剤 | |
| ES2386590T3 (es) | Inhibidores del virus de la hepatitis C | |
| TWI501957B (zh) | Ｃ型肝炎病毒抑制劑 | |
| JP5619289B2 (ja) | Ｃ型肝炎ウイルス阻害剤 | |
| US11607396B2 (en) | Bicyclic amide compounds and methods of use thereof | |
| KR20200030558A (ko) | 이환형 케톤 화합물 및 이의 사용 방법 | |
| US20130085141A1 (en) | SUBSTITUTED OCTAHYDROPYRROLO[1,2-a]PYRAZINE SULFONAMIDES AS CALCIUM CHANNEL BLOCKERS | |
| JP2023524207A (ja) | Ｎｒｆ２活性化剤としてのテトラヒドロイソキノリン化合物 | |
| WO2021214470A1 (en) | Tetrahydroisoquinoline compounds as nrf2 activators | |
| EA045906B1 (ru) | Терапевтические соединения | |
| TW202325286A (zh) | 治療性雙官能化合物 |